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.

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.

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.

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.

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.