Cardiovascular Remodeling Post-Ischemia: Herbs, Diet, and Drug Interventions.

Cardiovascular disease (CVD) is a serious health burden with increasing prevalence, and CVD continues to be the principal global source of illness and mortality. For several disorders, including CVD, the use of dietary and medicinal herbs instead of pharmaceutical drugs continues to be an alternate therapy strategy. Despite the prevalent use of synthetic pharmaceutical medications, there is currently an unprecedented push for the use of diet and herbal preparations in contemporary medical systems. This urge is fueled by a number of factors, the two most important being the common perception that they are safe and more cost-effective than modern pharmaceutical medicines. However, there is a lack of research focused on novel treatment targets that combine all these strategies-pharmaceuticals, diet, and herbs. In this review, we looked at the reported effects of pharmaceutical drugs and diet, as well as medicinal herbs, and propose a combination of these approaches to target independent pathways that could synergistically be efficacious in treating cardiovascular disease.

Neurotoxic and behavioral deficit in Drosophila melanogaster co-exposed to rotenone and iron.

Exposure to environmental toxicants has been linked with the onset of different neurodegenerative diseases in animals and humans. Here, we evaluated the toxic effects of co-exposure to iron and rotenone at low concentrations in Drosophila melanogaster. Adult wild-type flies were orally exposed to rotenone (50.0 µM) and ferrous sulfate (FeSO4; 1.0 and 10.0 µM) through the diet for 10 days. Thereafter, we evaluated markers of oxidative damage (Hydrogen Peroxide (H2O2), Nitric Oxide (NO), Protein Carbonyl, and malondialdehyde (MDA)), antioxidant status (catalase, Glutathione S-Transferase (GST), Total Thiol (T-SH) and Non-protein Thiol (NPSH), neurotransmission (monoamine oxidase; MAO and acetylcholinesterase, AChE) and mitochondrial respiration. The results indicated that flies fed rotenone and FeSO4 had impaired locomotion, reduced survival rate, and AChE activity with a corresponding increase in MAO activity when compared with the control (p < 0.05). Furthermore, rotenone and FeSO4 significantly decreased the antioxidant status with a concurrent accumulation of NO, MDA, and H2O2. Additionally, the activity of complex 1 and mitochondria bioenergetic capacity was compromised in the flies. These findings suggest that the combination of rotenone and FeSO4 elicited a possible synergistic toxic response in the flies and therefore provided further insights on the use of D. melanogaster in toxicological studies.

Induction of aggression and anxiety-like responses by perfluorooctanoic acid is accompanied by modulation of cholinergic- and purinergic signaling-related parameters in adult zebrafish.

Perfluorooctanoic acid (PFOA) is a contaminant of global concern owing to its prevalent occurrence in aquatic and terrestrial environments with potential hazardous impact on living organisms. Here, we investigated the influence of realistic environmental concentrations of PFOA (0, 0.25, 0.5, or 1.0 mg/L) on relevant behaviors of adult zebrafish (Danio rerio) (e.g., exploration to novelty, social preference, and aggression) and the possible role of PFOA in modulating cholinergic and purinergic signaling in the brain after exposure for 7 consecutive days. PFOA significantly increased geotaxis as well as reduced vertical exploration (a behavioral endpoint for anxiety), and increased the frequency and duration of aggressive episodes without affecting their social preference. Exposure to PFOA did not affect ADP hydrolysis, whereas ATP and AMP hydrolysis were significantly increased at the highest concentration tested. However, AChE activity was markedly decreased in all PFOA-exposed groups when compared with control. In conclusion, PFOA induces aggression and anxiety-like behavior in adult zebrafish and modulates both cholinergic and purinergic signaling biomarkers. These novel data can provide valuable insights into possible health threats related to human activities, demonstrating the utility of adult zebrafish to elucidate how PFOA affects neurobehavioral responses in aquatic organisms.

Diet, herbs and erectile function: A good friendship!

Plants and plant materials have been used for thousands of years to treat and control erectile dysfunction in men. This practice has spanned many cultures and traditions around the world, with the therapeutic effects of many plants attributed to their phytochemical constituents. This review explains how polyphenols (including phenolic acids, flavonoids, terpenoids, carotenoids, alkaloids and polyunsaturated fatty acids) in plants and plant food products interact with key enzymes (phosphodiesterase-5 [PDE-5], angiotensin-converting enzyme [ACE], acetylcholinesterase [AChE], adenosine deaminase [ADA] and arginase) associated with erectile dysfunction. By modulating or altering the activity of these physiologically important enzymes, various bioactive compounds from plants or plant products can synergistically or additively provide tremendous protection against male erectile problems.

Quercetin boosts nitric oxide levels and modulates the activities of arginase, acetylcholinesterase and adenosine deaminase in the corpus cavernosum of cyclosporine-treated rats.

One of the primary causes of erectile dysfunction (ED) in males is cardiovascular disease, such as hypertension (HT). As a result, the goal of this study is to see how quercetin (Q) affects the important biochemical parameters (nitric oxide, endogenous antioxidant enzymes)/specific enzymes (arginase, acetylcholinesterase and adenosine deaminase) linked to be responsible for smooth muscle relaxation in respect to sexual function. Wistar male rats (30) weighing 200-250 g were placed into five groups at random as follows: normal control group given normal saline (CTRL), hypertensive rats administered 25 mg/kg/day cyclosporine classified as ED group (HT), positive control administered Sildenafil (SIL, 5 mg/kg/day), quercetin (Q) 25 mg/kg/day (25 Q) and Q 50 mg/kg/day (50 Q). For 30 days, cyclosporine was administered i.p., while Q therapy was orally. HT was confirmed before the Q therapy after which the experimental rats were subjected to euthanasia. Nitric oxide (NO) levels, as well as enzymes [Superoxide dismutase, catalase, arginase, acetylcholinesterase (AChE) and adenosine deaminase (ADA)], were measured in the corpus cavernosum. Cyclosporine elevated arginase, AChE and ADA activity while lowering NO levels. Compared to the control group, Q of both concentrations reduced the activity of these enzymes and improved antioxidant status and NO levels. Thus, one of the mechanisms of action via which Q acts in the management of ED could be its ability to modulate these important enzymes and boost NO production.

Role of purinergic system and vitamin D in the anti-cancer immune response.

For several years, scientists have recognized that vitamin D plays an important role in mineral and bone homeostasis. It was mostly used to treat osteoporosis and rickets in the past decades. Vitamin D has also been discovered to be modulator of the immune system and may play a role in a variety of diseases, including autoimmune diseases, in recent years. Vitamin D interaction with the vitamin D receptor (VDR), which has transcriptional imparts and is displayed on a variety of cell types, including those of the immune system, appears to be accountable for the immune-modulating effects. The action of tumor cells and vitamin D were the first to be investigated, but the spotlight is now on immunologic and purinergic systems. We conducted a systematic search in Pub Med as well as Google scholar for studies written in English. Vitamin D, cancer, purinergic signaling, and immune response were among the search words. Vitamin D has the potential to be a useful coadjuvant in cancer therapy and the purinergic system may be a potential treatment target to cancer therapy, according to our findings.

Dietary supplementation of tiger nut alters biochemical parameters relevant to erectile function in l-NAME treated rats.

Tiger nut tubers have been reportedly used for the treatment of erectile dysfunction (ED) in folk medicine without scientific basis. Hence, this study evaluated the effect of tiger nut on erectile dysfunction by assessing biochemical parameters relevant to ED in male rats by nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) treatment. Rats were divided into five groups (n = 10) each: Control group; l-NAME plus basal diet; l-NAME plus Sildenafil citrate; diet supplemented processed tiger nut (20%) plus l-NAME;diet supplemented raw tiger nut (20%) plus l-NAME. l-NAME pre-treatment (40 mg/kg/day) lasted for 14 days. Arginase, acetycholinesterase (AChE) and adenosine deaminase (ADA) activities as well as nitric oxide levels (NO) in serum, brain and penile tissue were measured. l-NAME increased the activity of arginase, AChE and ADA and reduced NO levels. However, dietary supplementation with tiger nut caused a reduction on the activities of the above enzymes and up regulated nitric oxide levels when compared to the control group. The effect of tiger nut supplemented diet may be said to prevent alterations of the activities of the enzymes relevant in erectile function. Quercetin was revealed to be the most active component of tiger nut tuber by HPLC finger printing.

Tiger nut and walnut extracts modulate extracellular metabolism of ATP and adenosine through the NOS/cGMP/PKG signalling pathway in kidney slices.

BACKGROUND: Tiger nut (Cyperus esculentus L.) and walnut (Tetracarpidium conophorum Müll. Arg.) have been reportedly used in the treatment of inflammatory diseases such as atherosclerosis, prevent heart attack and improve blood circulation, reduce serum cholesterol level as well as inhibit oxidation reactions. PURPOSE: This study investigated the effect of tiger nut and walnut hydro-alcoholic extracts on extracellular metabolism of ATP through the NOS/cGMP/PKG signaling pathway induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) in kidney slices. METHODS: The plants were extracted for 24 h in 10 ml of 70% ethanol and 30% distilled water per gram milled material on a mechanical shaker and filtered using Whatman filter paper. The effect of the extracts on ecto-nucleotidases (NTPDase and 5' nucleotidase) and adenosine deaminase activities, nitrites and nitrates levels (NO, markers of NO production) as well as lipid and protein oxidation reactions in kidney slices were evaluated. Also, the phenolic components of the nut samples were determined using High Performance Liquid Chromatography (HPLC). RESULTS: The results revealed a protective effect of tiger nut and walnut on co-incubation with L-NAME of the enzyme activities, increased NO significantly (P < 0.05) when compared to the vehicle. L-NAME also increased the thiobabituric reactive substances but co-incubation with the extracts caused a significant reduction while protein oxidation across groups showed no significant difference when compared to the vehicle group. HPLC finger printing revealed the presence of quercetin and kaempferol as the most abundant phenolic compounds in tiger nut and walnut respectively. CONCLUSION: Tiger nut and walnut extracts showed a protective effect on L-NAME induced kidney slices by reducing the activities of NTPDase (ATP as substrate) and adenosine deaminase, increased NO levels as well as prevent oxidative damage. The effect observed may be attributed to the phenolic compounds present in both nuts as depicted by HPLC finger printing.

Aqueous extract of Securidaca longipendunculata Oliv. and Olax subscropioidea inhibits key enzymes (acetylcholinesterase and butyrylcholinesterase) linked with Alzheimer's disease in vitro.

CONTEXT: Plants have historically been used to treat neurodegerative diseases which include Alzheimer's disease. OBJECTIVE: This study investigated the antioxidant properties and inhibitory effect of aqueous extracts of Securidaca longipendunculata root and Olax subscropioidea leaf on the cholinergic system in rat brain in vitro. MATERIALS AND METHODS: Aqueous extracts (1:20 w/v) of S. longipendunculata root and O. subscropioidea leaf was prepared and the ability of the extract to inhibit the activities of acetylcholinesterase and butyrylcholinesterase was evaluated as well as antioxidants as typified by 2,2-azino-bis-(3-ethylbenthiazoline-6-sulphonic acid (ABTS•) radical scavenging ability and Fe chelation spectophotometrically. RESULTS: ABTS• radical scavenging ability showed that S. longipendunculata (0.075 Mmol TEAC/100 g) had a higher scavenging ability than O. subscropioidea (0.07 Mmol TEAC/100 g). Also, the Fe2+ chelating ability of both extracts revealed that S. longipendunculata (IC50 = 105.57 g/mL) had a significantly (p < 0.05) higher Fe2+ chelating ability than O. subscropioidea (IC50 = 255.84 g/mL). Extracts of S. longipendunculata and O. subscropioidea inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities. However, S. longipendunculata (IC50 = 108.02 g/mL) has the higher AChE inhibitory activity than O. subscropioidea (IC50 = 110.35 g/mL). Also, both extracts inhibit BChE activity in vitro but S. longipendunculata (IC50 = 82.55 g/mL) had a higher BChE inhibitory activity than O. subscropioidea (IC50 = 108.44 g/mL). DISCUSSION AND CONCLUSIONS: The mechanism by which S. longipendunculata root and O. subscropioidea leaf perform their anti-Alzheimer's disease activity may be by their inhibition on the key enzymes linked to this disease.

Neuroprotective effects of quercetin on memory and anxiogenic-like behavior in diabetic rats: Role of ectonucleotidases and acetylcholinesterase activities.

The present study investigated the protective effect of quercetin (Querc) on memory, anxiety-like behavior and impairment of ectonucleotidases and acetylcholinesterase (AChE) activities in brain of streptozotocin-induced diabetic rats (STZ-diabetes). The type 1 diabetes mellitus was induced by an intraperitoneal injection of 70mg/kg of streptozotocin (STZ), diluted in 0.1M sodium-citrate buffer (pH 4.5). Querc was dissolved in 25% ethanol and administered by gavage at the doses of 5, 25 and 50mg/kg once a day during 40days. The animals were distributed in eight groups of ten animals as follows: vehicle, Querc 5mg/kg, Querc 25mg/kg, Querc 50mg/kg, diabetes, diabetes plus Querc 5mg/kg, diabetes plus Querc 25mg/kg and diabetes plus Querc 50mg/kg. Querc was able to prevent the impairment of memory and the anxiogenic-like behavior induced by STZ-diabetes. In addition, Querc prevents the decrease in the NTPDase and increase in the adenosine deaminase (ADA) activities in SN from cerebral cortex of STZ-diabetes. STZ-diabetes increased the AChE activity in SN from cerebral cortex and hippocampus. Querc 50mg/kg was more effective to prevent the increase in AChE activity in the brain of STZ-diabetes. Querc also prevented an increase in the malondialdehyde levels in all the brain structures. In conclusion, the present findings showed that Querc could prevent the impairment of the enzymes that regulate the purinergic and cholinergic extracellular signaling and improve the memory and anxiety-like behavior induced by STZ-diabetes.

Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside-induced lipid peroxidation in rat pancreas by water-extractable phytochemicals from unripe pawpaw fruit (Carica papaya).

BACKGROUND: Various parts of unripe pawpaw (Carica papaya Linn) fruit have been reportedly used for the management or treatment of diabetes mellitus in folklore medicine. Therefore, the present study sought to investigate the inhibitory effects of the aqueous extract of different parts of unripe pawpaw fruit on key enzymes linked to type 2 diabetes (α-amylase and α-glucosidase) and sodium nitroprusside (SNP)-induced lipid peroxidation in rat pancreas in vitro. METHODS: The aqueous extracts of the unripe pawpaw (C. papaya) fruit parts were prepared (1:20 w/v) and the ability of the extracts to inhibit α-amylase, α-glucosidase and SNP-induced lipid peroxidation in rat pancreas in vitro was investigated. RESULTS: The results revealed that all the extracts inhibited α-amylase (IC50=0.87-1.11 mg/mL), α-glucosidase (IC50=1.76-2.64 mg/mL) and SNP-induced lipid peroxidation (IC50=1.99-2.42 mg/mL) in a dose-dependent manner. However, combination of the flesh, seed and peel in equal amounts had the highest inhibitory effect on α-amylase and α-glucosidase activities. CONCLUSIONS: Strong inhibitory activities of the unripe pawpaw fruit against key enzymes linked to type 2 diabetes and SNP-induced lipid peroxidation in rat pancreas could be part of the mechanism by which unripe pawpaw is used in the management/prevention of diabetes mellitus in folk medicine. However, combining the unripe pawpaw fruit parts in equal amounts exhibited synergistic properties on α-amylase and α-glucosidase inhibitory activities.

Inhibitory effect of aqueous extract of different parts of unripe pawpaw (Carica papaya) fruit on Fe²âº-induced oxidative stress in rat pancreas in vitro.

CONTEXT: Carica papaya L. (Caricaceae) is widespread throughout tropical Africa; it is cultivated for its fruits and it is eaten in various ways. OBJECTIVE: This study sought to investigate the inhibitory effect of the aqueous extract of different parts of unripe pawpaw fruit on Fe²âº-induced lipid peroxidation in rat's pancreas in vitro. MATERIALS AND METHODS: The aqueous extract of the unripe pawpaw fruit parts; peel (PG), seed (SG), flesh (FG), flesh with peel (FPG) and a combination of equal amount of all parts (CG) were prepared, the total phenolic content and the antioxidant activities of the extracts were then evaluated using various spectrophotometric methods. RESULT: PG had the highest total phenol content (1.24 mg GAE/g), flavonoid content (0.63 mg QUE/g), reducing power (7.07 mg AAE/g) and Fe²âº chelating ability while the SG had the highest 1,1-diphenyl-2-picrylhydrazyl radical scavenging ability. Furthermore, all the extracts caused a significant decrease (p < 0.05) in the malondialdehyde contents in the pancreas with SG (IC50 = 4.25 mg/mL) having the highest inhibitory effect on Fe²âº-induced lipid peroxidation. DISCUSSION AND CONCLUSION: This protective effect of the extracts on Fe²âº-induced lipid peroxidation in rat pancreas could be attributed to their phenolic compounds and, the possible mechanism may be through their antioxidant activities. However, the effect of combination of different parts of unripe pawpaw fruit in equal amount (w/w) on the inhibition of Fe²âº-induced lipid peroxidation in rat pancreas exhibited additive properties.