Oxidative Stress, Endoplasmic Reticulum Stress and Apoptosis in the Pathology of Alzheimer's Disease.

Alzheimer's disease (AD) accounts for a major statistic among the class of neurodegenerative diseases. A number of mechanisms have been identified in its pathogenesis and progression which include the amyloid beta (Aß) aggregation, hyperphosphorylation of tau protein, oxidative stress, endoplasmic reticulum (ER) stress and apoptosis. These processes are interconnected and contribute significantly to the loss of neurons, brain mass and consequential memory loss and other cognitive difficulties. Oxidative stress in AD appears to be caused by excess of oxygen free radicals and extracellular Aß deposits that cause local inflammatory processes and activate microglia, another possible source of reactive oxygen species (ROS). ER Stress describes the accumulation of misfolded and unfolded proteins as a result of physiological and pathological stimuli including high protein demand, toxins, inflammatory cytokines, and mutant protein expression that disturbs ER homeostasis. When compared to age-matched controls, postmortem brain tissues from AD patients showed elevated levels of ER stress markers, such as PERK, eIF2α, IRE1α, the chaperone Grp78, and the downstream mediator of cell death CHOP. Apoptosis is in charge of eliminating unnecessary and undesired cells to maintain good health. However, it has been demonstrated that a malfunctioning apoptotic pathway is a major factor in the development of certain neurological and immunological problems and diseases in people, including neurodegenerative diseases. This article highlights and discussed some of the experimentally established mechanisms through which these processes lead to the development as well as the exacerbation of AD.

GC-MS analysis of aqueous extract of Nymphaea lotus and ameliorative potential of its biosynthesized gold nanoparticles against cadmium-induced kidney damage in rats.

Plants possess compounds serving as reducing agents for green synthesis of gold nanoparticles (AuNPs), which is currently considered for biomedical application. Exposure to cadmium (Cd) can affect the functional integrity of the several organs such as kidney and liver. Nymphaea lotus (NL) is known for its several medicinal properties, including its protective role against tissue damages. This study investigated the bioactive compounds in NL using gas chromatography-mass spectroscopy (GC-MS) and ameliorative potential of its biosynthesized AuNPs (NL-AuNPs) against Cd-induced nephrotoxicity in rats. The presence of bioactive compounds in N. lotus was investigated by GC-MS in aqueous extract of NL. Gold nanoparticles were synthesized using aqueous extract of NL. Thirty rats were grouped into six (n = 5). Group 1 served as control, while group 2, 3, 4 and 5 received CdCl2 (10 mg/kg) orally for five days. Thereafter, groups 3, 4, and 5, respectively, received silymarin (75 mg/kg), 5 and 10 mg/kg NL-AuNPs, orally for 14 days, while group 6 received 10 mg/kg NL-AuNPs only. Rats were sacrificed after treatment, and biochemical parameters and kidney histopathology were evaluated. Bioactive compounds of pharmacological importance identified include pyrogallol, oxacyclohexadecan-2-one, 22-Desoxycarpesterol, 7,22-Ergostadienol, ß-sitosterol and Dihydro-ß-agarofuran. Cadmium caused nephrotoxicity in rats, as evidenced by significant (p < 0.05) increase in the levels of kidney function markers (serum urea and creatinine) and inflammatory markers (Interleukin-6 (IL-6) and Nuclear Factor-κB (NF-κB)) when compared with control. These changes were significantly (p < 0.05) ameliorated by the spherically-synthesized NL-AuNPs (25-30 nm) with the 5 mg/kg NL-AuNPs more potent against kidney damage induced by Cd in rats but high doses of NL-AuNPs (≥10 mg/kg) could be suggested toxic. NL possess phytochemicals capable of reducing gold salts to nanoparticle form, and doses up to 5 mg/kg could be considered safe for the treatment of renal damage occasioned by cadmium.

Bioactivities of Garcinia kola enzymatic hydrolysates at different enzyme-substrate ratios.

Natural products, such as enzymatic hydrolysates and bioactive peptides from dietary sources, are safe alternatives to synthetic compounds linked to various deleterious effects. The purpose of this study is to determine the in vitro bioactivities (antioxidant and anti-inflammatory activities) of Garcinia kola seeds enzymatic hydrolysates (GKPHs) at different enzyme (pepsin)-substrate ratios. G. kola protein, isolated by alkaline solubilization and acid precipitation, was hydrolyzed with pepsin at varying enzyme-substrate (E:S) ratios. The antioxidant parameters investigated include 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical scavenging, hydrogen peroxide scavenging and ferrous ion (Fe2+) chelating activities. For anti-inflammatory properties, membrane stabilization and protein denaturation activities tests were used. GKPH produced at 1:32 had the highest degree of hydrolysis (66.27 ± 4.21%). All GKPHs had excellent in vitro anti-inflammatory properties. However, only enzymatic hydrolysates produced at 1:16 (E:S) ratio chelated iron (II) and as well had the highest percentage hemolysis inhibition of 84.45 ± 0.007%, percentage protein denaturation inhibition of 53.36 ± 0.01% at maximum concentration and exhibited highest DPPH scavenging activity (87.24 ± 0.10%). The enzymatic hydrolysates had excellent solubility, emulsifying and foaming properties. It could be deduced from this study that pepsin at a ratio of 1:16 of G. kola protein produced the most effective enzymatic hydrolysates in terms of their antioxidant and anti-inflammatory activities. G. kola pepsin enzymatic hydrolysates, thus, have potential in development as functional foods and as therapeutics pharmaceutical industries in the management of diseases associated with oxidative stress and inflammation owing to their excellent functional, antioxidant and anti-inflammatory properties.

In vitro antioxidant and anti-inflammatory properties of Artocarpus altilis (Parkinson) Fosberg (seedless breadfruit) fruit pulp protein hydrolysates.

Protein hydrolysates from dietary sources possess many physiological and biological properties. Artocarpus altilis is an evergreen multipurpose plant with many benefits. Therefore, this study evaluates in vitro antioxidant and anti-inflammatory properties of A. altilis protein hydrolysates. Protein was isolated from A. altilis and hydrolysed with pepsin and trypsin separately using different enzyme: substrate ratios (1:8, 1:16, 1:32). Antioxidant properties investigated included Fe2+-chelating, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and hydrogen peroxide radical scavenging activities. Anti-inflammatory activities were determined using effects on hypotonic solution-induced cell lysis on red blood cell membrane stabilisation and heat-induced protein denaturation. The degree of hydrolysis of trypsin hydrolysate increased with increasing enzyme-substrate ratio, while pepsin hydrolysate decreased as the enzyme-substrate ratio increased. The dominant amino acids in A. altilis protein and hydrolysates were glutamate, aspartate and leucine. Protein hydrolysates obtained from pepsin and trypsin digestion had DPPH scavenging abilities of 43.0 ± 0.01% and 22.2 ± 0.01%, respectively. However, trypsin-hydrolysed protein had a high Fe2+-chelating ability, while pepsin-hydrolysed protein had high hydrogen peroxide scavenging ability. Trypsin-hydrolysed protein showed good membrane stability and inhibition of protein denaturation. The results indicated that A. altilis protein hydrolysates possess significant antioxidant and anti-inflammatory effects and can further lend support to food industries as functional foods.

Synthesized gold nanoparticles mediated by Crassocephalum rubens extract down-regulate KIM-1/NGAL genes and inhibit oxidative stress in cadmium-induced kidney damage in rats.

Cadmium (Cd) exposure induces kidney damage by mediating oxidative stress and inflammation. In this study, the role of Crassocephalum rubens-gold nanoparticles (C. rubens-AuNPs) in down-regulating kidney injury molecules-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) genes and inhibiting oxidative stress in Cd-induced kidney damage in rats was investigated. Thirty male Wistar rats were distributed randomly into six groups (n = 5). Group I served as control, while groups II, III, IV, and V rats were administered with 20 mg/kg b.w. cadmium chloride (CdCl2) for five consecutive days. Groups III, IV, and V rats were treated, 24 h after the last dose of CdCl2, with silymarin, 5 mg/kg and 10 mg/kg C. rubens-AuNPs, respectively, for 14 days. Group VI rats received 10 mg/kg C. rubens-AuNPs only for 14 days. Animals were sacrificed 24 h after the last dose of the treatment. Biochemical parameters such as kidney function markers, biomarkers of nephrotoxicity, and oxidative stress markers were assayed. Results indicated that 20 mg/kg b.w. CdCl2 caused kidney damage, as evidenced by significant (p < 0.05) increase in the levels of serum urea and creatinine, malondialdehyde, reduced level of superoxide dismutase (SOD), and increased mRNA expression of the kidney injury biomarkers (KIM-1 and NGAL genes), when compared with the control. However, these changes were attenuated by both doses of C. rubens-AuNPs when compared with Cd-induced nephrotoxic rats. It can be suggested that C. rubens-AuNPs have the potential to ameliorate kidney damage induced by Cd via oxidative stress inhibition and down-regulation of KIM-1/NGAL genes.

Short- and long-term effect of colorectal cancer targeting peptides conjugated to gold nanoparticles in rats' liver and colon after single exposure.

Peptides play important roles in the diagnosis, prognostic predictors, and treatment of various kinds of cancer. Peptides (p.C, p.L and p.14), derived from the phage display peptide libraries, specifically binds to colorectal cancer (CRC) cells in vitro. To allow tumor specificity and selectivity for in vivo diagnosis of CRC, biotinylated p.C, p.L and p.14 were conjugated to AuNPs (14 nm) via the biotin-streptavidin interaction. Male Wistar rats were intravenously injected with a single dose (100 µg/kg body weight) of AuNPs (citrate-AuNPs, PEG-AuNPs, p.C-PEG-, p.L-PEG- and p.14-PEG-AuNPs). Animals were monitored for behavioral changes, and sacrificed either 14 days or 84 days post-injection. Biochemical changes, oxidative stress, and histology of the liver and colon were assessed. No significant changes were noted in the rats injected with all the AuNPs, except p.L-PEG-AuNPs that caused significant toxicity (p < 0.05) 14 days post-exposure when compared to control group, as evidenced by increased relative liver weight, increased malondialdehyde levels and histological changes in the liver. These changes, however, returned to normalcy 84 days post-injection. It can be concluded, based on these findings, that p.L induced a transient toxicity in rats after a single intravenous injection, and can therefore be considered non-toxic long-term after a single exposure.

Ameliorating activity of polyphenolic-rich extracts of Basella rubra L. leaves on pancreatic ß-cell dysfunction in streptozotocin-induced diabetic rats.

OBJECTIVES: To assess the ameliorative activity of polyphenolic-rich extracts of Basella rubra leaves on ß-cell dysfunction in type-II diabetes (T2DM). METHODS: Total phenolic and flavonoid contents; α-amylase and α-glucosidase inhibitory actions and qualitative analysis of the bioactive compounds of the polyphenolic-rich extract of B. rubra leaves were investigated using gas chromatography-mass spectroscopy (GC-MS). Diabetes mellitus (DM) was induced by single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and the rats were orally given bound phenolic (BPE) and free phenolic extracts (FPE) of B. rubra (B.R) leaves at 200 and 400 mg/kg b.w once daily for 14 days. Biochemical analyses were executed for evaluation of serum insulin, serum lipid profile concentrations, liver enzymes activities. RESULTS: The extracts demonstrated antioxidant potentials and enzymes inhibitory activities in dose dependent manner; and several bioactive compounds as revealed by GC-MS. BPE and FPE considerably (p<0.05) reduced hyperglycemia, improved serum insulin levels, ameliorated the concentration of serum lipid profiles and improved liver antioxidant activities. Additionally, BPE and FPE expressively decreased alanine aminotransferases (ALT), aspartate aminotransferases (AST), gamma-glutamyl transferase (GGT) activities along with levels of bilirubin and urea when compare to diabetic control rats. CONCLUSIONS: Data acquired exhibited the ability of BPE and FPE to improve pancreatic beta-cell in streptozotocin-induced rats.

Combined effect of metformin and gallic acid on inflammation, antioxidant status, endoplasmic reticulum (ER) stress and glucose metabolism in fructose-fed streptozotocin-induced diabetic rats.

Over time, diabetes patients usually need combination therapy involving two or more agents, including phytonutrients to attain therapeutic targets. The purpose of this research is to elucidate the combined effect of metformin and gallic acid (GA) on glucose metabolism, inflammation as well as oxidative and endoplasmic reticulum (ER) stresses in fructose-fed diabetic rats. Thirty-five rats of Wistar strain were arbitrarily distributed into five groups, each containing seven animals as follows: normal control, diabetic control, groups administered 100 mg/kg bw metformin only, 50 mg/kg bw gallic acid only and a combination of both. Experimental animals were made diabetic by single injection of 40 mg/kg streptozotocin (intraperitoneally) subsequent to 14 days administration of 10 % fructose prior. Treatment of rats continued for 21 days following diabetes confirmation. Glucose and insulin levels as well as lipid profile were evaluated in the serum, while activities of catalase and superoxide dismutase were estimated in both liver and pancreas. In addition, levels of malondialdehyde, interleukin-6 and tumor necrosis factor-alpha, as well as expression of activating transcription factor-4 were evaluated in liver and pancreas of diabetic rats. Activities of glucose-6-phosphatase and glucokinase were also determined in liver of diabetic animals. Metformin only, GA only and combination of metformin and GA significantly improved antioxidant status and glucose homeostasis while inflammation and endoplasmic reticulum stress were significantly ameliorated in diabetic rats. Metformin/GA combination appeared to improve glucose metabolism by increasing insulin level and ameliorating the dysregulated activities of glucose metabolizing enzymes and ER stress better than either metformin only or GA only. It could be concluded that coadministration of metformin/GA produced a combined effect in ameliorating diabetes in Wistar rats and could be considered in treatment of diabetes.

In vitroanti-oxidant and cytotoxic activities of gold nanoparticles synthesized from an aqueous extract of theXylopia aethiopicafruit.

The development of gold nanoparticles (AuNPs) using a green approach has drawn considerable interest in the field of nanomedicine. Its wide application in clinical diagnosis, imaging and therapeutics portrays its importance for human existence. In this study, we reported on the biogenic synthesis of AuNPs using the aqueous extract of theXylopia aethiopicafruit (AEXAf), which acts as both a reducing and stabilizing agent. The characterization of AEXAf-AuNPs was performed using ultraviolet-visible spectroscopy, dynamic light scattering and zeta potential measurements, high-resolution transmission electron microscopy and Fourier transform-infrared spectroscopy. Thein vitroanti-oxidant activities of the AEXAf-AuNPs and AEXAf were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing anti-oxidant power. Thein vitrocytotoxic activities of the AEXAf-AuNPs and AEXAf against breast and colorectal cancer cells were evaluated using 3,-(4,5 dimethylthiazol)-2,5 diphenyl tetrazolium bromide (MTT) viability and annexin V/PI assays. The AEXAf-AuNPs exhibited surface plasmon absorption maximum at 522 nm and were stable for 4 weeks. The average size of the AEXAf-AuNPs was 10.61 ± 3.33 nm on the high-resolution transmission electron microscopy images. Thein vitroanti-oxidant activities of the AEXAf-AuNPs and AEXAf were concentration dependent. The AEXAf-AuNPs were cytotoxic to the cancer cells and non-toxic to the non-cancerous human fibroblast cells (KMST-6) (up to 200µg ml-1). From these results, the AEXAf-AuNPs showed good anti-oxidant and anti-cancer activities, and can be suggested as a possible therapeutic agent for breast and colorectal cancer.

Investigation of bioactive compounds in Crassocephalum rubens leaf and in vitro anticancer activity of its biosynthesized gold nanoparticles.

The development of cancer therapies has become difficult due to high metastasis, and lack of tissue selectivity, which in most cases affects normal cells. Demand for anticancer therapy is therefore increasing on daily basis. Gold nanoparticles (AuNPs) have many applications in biomedical field. Biological synthesis of AuNPs using aqueous extract of Crassocephalum rubens (AECR) was designed to investigate the in vitro anticancer potential. The synthesized AuNPs were characterized by UV-vis spectroscopy, high-resolution transmission electron microscopy, and Fourier transform infrared spectroscopy. The characterization results showed the formation of green AuNPs of wavelength 538 nm, and mostly spherical AuNPs with 20 ±â€¯5 nm size. Significant anticancer activity of the AECR-AuNPs on MCF-7 and Caco-2 cells was noted at higher concentrations (125 and 250 µg/mL) during 24 and at all concentrations tested during 48 h. It can therefore be concluded that AECR leaves can mediate stable AuNPs with anticancer properties.

Biological synthesis of gold and silver nanoparticles using leaf extracts of Crassocephalum rubens and their comparative in vitro antioxidant activities.

The use of plant and plant products in the synthesis of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) is made possible because of the natural inherent phytochemicals responsible for the reduction of respective metallic salts to nanoparticle forms, and ensuring therapeutic applicability. In this study, synthesis of AgNPs and AuNPs was performed using two different aqueous extraction methods for Crassocephalum rubens: maceration using laboratory method of extraction (cold aqueous extract of Crassocephalum rubens (AECR)), and decoction using traditional healer's method of extraction (hot aqueous crude extract of Crassocephalum rubens (CECR)). The synthesized nanoparticles were characterized using various methods, and in vitro antioxidant potential were thereafter investigated. The characterization results indicated the formation of mostly spherical-shaped AgNPs and AuNPs with surface plasmon resonance (SPR) band of 470 nm and 540 nm, respectively. The nanoparticles possess high antioxidant potentials but AECR synthesized AuNPs exhibited the least phytochemical contents and antioxidant potential when compared to other nanoparticles. It can therefore be concluded that extraction method and nanoparticle type are important factors that could influence the antioxidant properties of the nanoparticles. Further studies using these nanoparticles as anticancer or anti-inflammatory agent in both in vitro and in vivo are underway.

Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2.

The emergence of coronavirus disease 2019 (COVID-19) in December 2019 has resulted in over 20 million cases and 741,808 deaths globally, affecting more than 200 countries. COVID-19 was declared a pandemic on 11 March 2020 by the World Health Organization. The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). There is limited information on COVID-19, and treatment has so far focused on supportive care and use of repurposed drugs. COVID-19 can be transmitted via person-to-person contact through droplet spread. Some of the recommended precautionary measures to reduce the rate of disease spread include social distancing, good hygiene practices, and avoidance of crowded areas. These measures are effective because the droplets are heavy and can only travel approximately 1 meter in the air, settling quickly on fixed surfaces. Promising strategies to combat SARS-CoV-2 include discovery of therapeutic targets/drugs and vaccines. In this review, we summarize the epidemiology, pathophysiology, and diagnosis of COVID-19. We also address the mechanisms of action of approved repurposed drugs for therapeutic management of the disease.

Metformin/Donepezil combination modulates brain antioxidant status and hippocampal endoplasmic reticulum stress in type 2 diabetic rats.

PURPOSE: Diabetes mellitus is associated with perturbations in brain biochemical parameters associated with dementia. This study aimed at comparing the effect of metformin and metformin/donepezil combination on oxidative stress, endoplasmic reticulum stress and inflammation in the brain of diabetic Wistar rats. METHODS: Diabetes was induced by single intraperitoneal injection of 40 mg/kg streptozotocin after administration of 10% fructose for 14 days. Animals were randomly assigned to four groups of five animals each. Group 1 was the normal control and received only distilled water. Groups 2 and 3 were diabetic rats treated with metformin/donepezil combination and metformin only respectively, while group 4 was diabetic control. Treatment lasted for 21 days after confirmation of diabetes. Activities of acetylcholinesterase (AchE), butyrylcholinesterase (BchE), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase were evaluated in the brain of diabetic rats. Enzyme-linked immunosorbent assay was used to estimate brain levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) malondialdehyde and glucose transporter-4 (GLUT4), while expression of endoplasmic reticulum stress markers - glucose regulated protein-78 (GRP78), activating transcription factor-4 (ATF4) and C/EBP homologous protein (CHOP) was determined using real-time PCR in the hippocampus of diabetic rats. RESULTS: Treatment with metformin/donepezil combination significantly reduced the activities of AchE, BchE as well as levels of malondialdehyde, TNF-α and IL-6, while the activities of SOD, GPx and catalase were significantly increased in the brain. Moreover, expression of ER stress markers was attenuated in the hippocampus. CONCLUSION: Metformin/donepezil combination appeared more efficacious than metformin only and could be considered for managing diabetes-associated dementia.

Antioxidant activities of peptide hydrolysates obtained from the seeds of Treculia africana Decne (African breadfruit).

Protein hydrolysates usually possess higher nutritive value than an equivalent mixture of free amino acids. This study was aimed at determining the antioxidant activities of protein hydrolysates of Treculia africana seeds. Soluble protein was isolated from Treculia africana seed flour by alkaline solubilization and acid precipitation, and further hydrolyzed with three proteases (trypsin, pancreatin and pepsin) individually and in a sequential two- and three-protease systems. Antioxidant activities (DPPH, FRAP and lipid peroxidation) of the hydrolysates were investigated. Hydrolysates from Treculia africana seed protein showed varying degree of hydrolysis, pancreatin hydrolysates had the highest (94.92%) and pancreatin-pepsin hydrolysates had the least (6.59%). Pancreatin proved to be the most efficient protease for hydrolyzing Treculia africana protein with a high protein recovery of 156.06 mg/ml. Its hydrolysates exhibited the highest DPPH scavenging activity (71.02%) and had a high radical-mediated peroxidation of oleic acid. Likewise, pancreatin hydrolysates as well as trypsin-pancreatin hydrolysates showed the highest FRAP activity (37.17 and 38.52 µg/ml BHA, respectively). Pancreatin hydrolysates showed significant higher (p < 0.05) antioxidant potentials than other hydrolysates of T. africana seed protein. These findings showed the potential use of Treculia africana hydrolysates as antioxidants in reducing food spoilage and management of oxidative stress-related metabolic disorders.

Prevention of short-term memory impairment by Bryophyllum pinnatum (Lam.) Oken and its effect on acetylcholinesterase changes in CCl4-induced neurotoxicity in rats.

Background Short-term memory impairment is a neurodegenerative disease associated with oxidative stress. Bryophyllum pinnatum (Lam.) Oken of the family Crassulaceae is traditionally used in the treatment of diseases, such as cough, wounds, and kidney diseases. This study evaluates the effect of the aqueous extract of B. pinnatum (AEBP) leaves on acetylcholinesterase activity in carbon tetrachloride (CCl4)-induced short-term memory impairment in rats. Methods Thirty male Wistar albino rats were used in this study and were divided into six groups (n=5). Group I served as control, group II rats were induced with CCl4, while groups III-V animals were pretreated with silymarin (25 mg/kg body weight), 25 and 50 mg/kg body weight AEBP leaves, respectively, once daily by oral gavage for 14 days prior to a single intraperitoneal injection of CCl4. Animals in group VI received 50 mg/kg body weight AEBP only by oral gavage. Results Administration of carbon tetrachloride significantly increased (p<0.05) spontaneous alternation and locomotor function in rats when compared with the control group. Also, the levels of acetylcholinesterase, adenosine deaminase, and malondialdehyde were increased in CCl4-administered rats, with reduction in both enzymatic and nonenzymatic antioxidant levels. However, pretreatment of rats with AEBP leaves, at tested doses, prevented these changes. Conclusions The increased antioxidant status and the inhibition of acetylcholinesterase activity show that AEBP leaves improve learning memory and stabilizes memory impairment caused by CCl4.

Toxicological Behavior of Gold Nanoparticles on Various Models: Influence of Physicochemical Properties and Other Factors.

Potential applications of gold nanoparticles in biomedicine have increasingly been reported on account of the ease of synthesis, bioinert characteristics, optical properties, chemical stability, high biocompatibility, and specificity. The safety of these particles remains a great concern, as there are differences among toxicity study protocols used. This article focuses on integrating results of research on the toxicological behavior of gold nanoparticles. This can be influenced by the physicochemical properties, including size, shape, surface charge, and other factors, such as methods used in the synthesis of gold nanoparticles, models used, dose, in vivo route of administration, and interference of gold nanoparticles with in vitro toxicity assay systems. Several researchers have reported toxicological studies with regard to gold nanoparticles, using various in vitro, in vivo, and in ovo models. The conflicting results concerning the toxicity of gold nanoparticles should thus be addressed to justify the safe use of gold nanoparticles in biomedicine.

Effect of dietary components on miRNA and colorectal carcinogenesis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers diagnosed and among the commonest causes of cancer-related mortality globally. Despite the various available treatment options, millions of people still suffer from this illness and most of these treatment options have several limitations. Therefore, a less expensive, non-invasive or a treatment that requires the use of dietary products remains a focal point in this review. MAIN BODY: Aberrant microRNA expression has been revealed to have a functional role in the initiation and progression of CRC. These has shown significant promise in the diagnosis and prognosis of CRC, owing to their unique expression profile associated with cancer types and malignancies. Moreover, microRNA therapeutics show a great promise in preclinical studies, and these encourage further development of their clinical use in CRC patients. Additionally, emerging studies show the chemo-preventive potential of dietary components in microRNA modulation using several CRC models. This review examines the dietary interplay between microRNAs and CRC incidence. Improving the understanding of the interactions between microRNAs and dietary components in the carcinogenesis of CRC will assist the study of CRC progression and finally, in developing personalized approaches for cancer prevention and therapy. CONCLUSION: Although miRNA research is still at its infancy, it could serve as a promising predictive biomarkers and therapeutic targets for CRC. Given the ever-expanding number of miRNAs, understanding their functional aspects represents a promising option for further research.

Bryophyllum pinnatum inhibits arginase II activity and prevents oxidative damage occasioned by carbon tetrachloride (CCl4) in rats.

Bryophyllum pinnatum (B. pinnatum) (Lam.) Oken is used in tropical Africa for the treatment of several diseases such as kidney and urinary disorders. This study was aimed to evaluate the effect of B. pinnatum on arginase II activity and its prevention against renal oxidative damage occasioned by CCl4 in rats. Rats were randomly divided into six groups; group I served as the control, group II served as carbon tetrachloride (CCl4) intoxicated group, group III-V animals were pre-treated with silymarin (25 mg/kg body weight), 25 mg/kg body weight aqueous extracts of Bryophyllum pinnatum (AEBP) and 50 mg/kg body weight AEBP, respectively, for 14 days, followed by a single injection of CCl4. Group VI rats received AEBP only (50 mg/kg body weight). Results obtained revealed that CCl4 intoxication significantly increased (p < 0.05) the levels of renal markers (serum urea, creatinine and arginase II) in rats when compared to the control group. Further, oxidative stress status appeared in CCl4-intoxicated rats, as evidence by significant elevation in malondialdehyde (MDA), with concomitant decrease in levels of functional sulfhydryl groups (SH), antioxidant enzymes and nitric oxide in rats' kidney. These adverse changes, due to CCl4 intoxication in rats, were however, prevented by pre-treatment with AEBP leaves (25 and 50 mg/kg body weight). The inhibition of arginase II, as well as increased antioxidant status by AEBP in CCl4-intoxicated rats suggests that B. pinnatum can protect kidney against CCl4-induced oxidative damage.

Evaluation of acute and subacute toxicity of aqueous extract of Crassocephalum rubens leaves in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Crassocephalum rubens is found throughout tropical Africa including the Indian Ocean islands. The leaves are commonly eaten in form of soups and sauces in South-Western Nigeria, also in other humid zones of Africa. Traditionally, it is used as an antidote against any form of poisoning; used to treat stomach and liver complaints; and externally to treat burns, sore eyes, earache, leprosy and breast cancer. In this study, acute and subacute toxicity of aqueous extract of C. rubens leaves was evaluated in rats in order to assess its safety profile. MATERIALS AND METHODS: In acute toxicity study, rats were given a single oral administration of aqueous extract of C. rubens leaves at graded doses (250-5000mg/kg). The animals were monitored for behavioural changes and possible mortality over a period of 24h and thereafter, for 14 days. In the subacute toxicity study, rats of both sexes were administered C. rubens orally at doses of 250mg/kg, 500mg/kg, 750mg/kg and 1000mg/kg body weight daily, for 28 days. Rats were observed weekly for any changes in general behaviour and body weights. In addition, other relevant parameters were assayed at the end of the main and reversibility study periods. RESULTS: There was no observed adverse effect; including mortality in the animals. The extract caused no significant difference in the body weights as well as organs weights of treated groups when compared with the control groups. Haematological and biochemical parameters also revealed no toxic effects of the extract on rats. Histological assessments were normal in liver and kidney. CONCLUSIONS: It can therefore be suggested based on the results from this study that aqueous extract of C. rubens leaves, at dosage levels up to 1000mg/kg, is non-toxic and could also offer protection on some body tissues. Aqueous extract of C. rubens could therefore, be considered safe. This study supports the application of Crassocephalum rubens in traditional medicine.