Babatunji Emmanuel Oyinloye

Reactive oxygen species, apoptosis, antimicrobial peptides and human inflammatory diseases.

Excessive free radical generation, especially reactive oxygen species (ROS) leading to oxidative stress in the biological system, has been implicated in the pathogenesis and pathological conditions associated with diverse human inflammatory diseases (HIDs). Although inflammation which is considered advantageous is a defensive mechanism in response to xenobiotics and foreign pathogen; as a result of cellular damage arising from oxidative stress, if uncontrolled, it may degenerate to chronic inflammation when the ROS levels exceed the antioxidant capacity. Therefore, in the normal resolution of inflammatory reactions, apoptosis is acknowledged to play a crucial role, while on the other hand, dysregulation in the induction of apoptosis by enhanced ROS production could also result in excessive apoptosis identified in the pathogenesis of HIDs. Apparently, a careful balance must be maintained in this complex environment. Antimicrobial peptides (AMPs) have been proposed in this review as an excellent candidate capable of playing prominent roles in maintaining this balance. Consequently, in novel drug design for the treatment and management of HIDs, AMPs are promising candidates owing to their size and multidimensional properties as well as their wide spectrum of activities and indications of reduced rate of resistance.

Anti-fatty liver effects of oils from Zingiber officinale and Curcuma longa on ethanol-induced fatty liver in rats

OBJECTIVE The present study is aimed at evaluating the protective effects of oils from Zingiber officinale (ginger) and Curcuma longa (turmeric) on acute ethanol-induced fatty liver in male Wistar rats. METHODS Ferric reducing antioxidant power activity and oxygen radical absorbance capacity of the oils were evaluated ex vivo. Rats were pretreated for 28 d with standard drug (Livolin Forte) and oils from Z. officinale and C. longa before they were exposed to 45% ethanol (4.8 g/kg) to induce acute fatty liver. Histological changes were observed and the degree of protection was measured by using biochemical parameters such as alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities. Serum triglyceride (TG) level, total cholesterol (TC) level and the effects of both oils on reduced gluthatione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) levels were estimated. RESULTS Oils from Z. officinale and C. longa at a dose of 200 mg/kg showed hepatoprotection by decreasing the activities of serum enzymes, serum TG, serum TC and hepatic MDA, while they significantly restored the level of GSH as well as GST and SOD activities. Histological examination of rats tissues was related to the obtained results. CONCLUSION From the results it may be concluded that oils from Z. officinale and C. longa (200 mg/kg) exhibited hepatoprotective activity in acute ethanol-induced fatty liver and Z. officinale oil was identified to have better effects than C. longa oil.

Prophylactic effect of aqueous extract of Sesamum indicum seeds on ethanol-induced toxicity in male rats

The liver is vulnerable to alcohol-related injury because it is the primary site of alcohol metabolism. Additionally, a number of potentially dangerous by-products are generated as alcohol is broken down in the liver. However, dietary supplements may prevent or relieve some of alcohols deleterious effects. Therefore, this study was conducted to evaluate the prophylactic effect of aqueous extract of Sesamum indicum (SI) on ethanol induced toxicity in rats. Male Wistar albino rats were divided into control, ethanol, pre-treatment, simultaneous and post-treatment groups. In the prophylactic experiment, Sesamum indicum, (200 mg/kg body weight) was administered by oral gavage for 28 days; two hours before, simultaneously with or two hours after ethanol exposure. Toxicity was induced by administering 45% ethanol (4.8 g/kg bw) by oral gavage. Lipid peroxidation (TBARS) and reduced glutathione (GSH) levels and catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and gluthathione-S-transferase (GST) activities were then determined in the liver, serum triglyceride (TG) levels, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were monitored and histological examination was carried out. The results revealed that ethanol administration led to significant elevation of TBARS level while depleting in the level of GSH as well as CAT, GPx, SOD and GST activities. Similarly, TG level and ALT and AST activities were elevated. The SI pre-treated group significantly inhibited TBARS, restored GSH level, enhanced CAT, GPx, SOD and GST activities and significantly decreased the elevated level of serum TG, ALT and AST activities. SI treatment (simultaneously with ethanol) exhibited similar effects to those of the SI pre-treated groups, while the SI post-treated group did not show the same protection as the Pre-treated group. S. indicum possesses antioxidant and hepatoprotective properties, that eliminate the deleterious effects of toxic metabolites of ethanol.

Protective effect of Irvingia gabonensis stem bark extract on cadmium-induced nephrotoxicity in rats.

ABSTRACT Cadmium has been considered a risk factor for humans as it accumulates in body tissues, such as the liver, lungs, kidneys, bones, and reproductive organs. The aim of the present study was to evaluate the effect of Irvingia gabonensis (IG) against cadmium (Cd)- induced nephrotoxicity. The study was performed on twenty (20) male rats divided into four groups: control group, cadmium group (4 mg/kg/day, intraperitoneally), cadmium + extract (200 mg/kg body weight by oral gavage) and cadmium + extract (400 mg/kg body weight by oral gavage). Changes in the kidney biochemical markers, namely glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), aminotransferase (ALT), aspartate aminotransferase (AST) activities and levels of malondialdehyde (MDA), urea, and creatinine were determined in serum. Histological examinations were monitored. Exposure to Cd lowered the activities of kidney antioxidants, while it increased LPO levels. Levels of all disrupted parameters were alleviated by co-administration of IG extract. The malondialdehyde concentration of the rats treated with 200 and 400 mg/kg body weight of the extract significantly decreased (p<0.05) compared with the untreated cadmium rats. Yet the creatinine concentration decreased significantly (p<0.05) when the cadmium animals treated with 200 and 400 mg/kg body weight of the extract were compared with the cadmium control. Furthermore, histological alterations in the kidney were observed in cadmium untreated rats and these were ameliorated in cadmium treated rats by co-administration of IG extract. IG showed apparent protective and curative effect on Cd-induced nephrotoxicity

The promise of antimicrobial peptides for treatment of human schistosomiasis.

Schistosomiasis sometimes referred to as bilharzia ranks high among the common neglected human tropical diseases. Parasitic trematode flatworm belonging to the genus Schistosoma is responsible for this acute and chronic disease. Its prevalence is rapidly increasing in the tropical regions worldwide; however, its economic and global health impact is grossly underestimated. There are five recognized species of schistosome parasitizing humans but the common species causing the disease are S. haematobium, S. japonicum and S. mansoni. Over the years, praziquantel, due to its advantage over other drugs employed in the treatment of schistosomiasis especially because of its effectiveness against all schistosoma species has remained the drug of choice. Unfortunately, due to drug pressure, some reports of praziquantel resistance in the treatment of some strains of S. haematobium and S. mansoni have been documented in literature. This has necessitated the search for novel anti-schistosomal agents as alternatives to praziquantel treatment. Currently, antimicrobial peptides are gaining prominence as possible sources of novel drugs in the control and treatment of schistosomiasis. A major driving force for evaluating antimicrobial peptides is their general diverse therapeutic applications, basically due to their size and properties as well as their broad spectrum of activities. Therefore, antimicrobial peptides are attractive candidates with promising results that may overcome drug resistance problems in search for novel therapeutic agents for the control and treatment of schistosomiasis.

Prophylactic Effects of Ethanolic Extract of Irvingia gabonensis Stem Bark against Cadmium-Induced Toxicity in Albino Rats

The prophylactic effect of ethanolic extract of Irvingia gabonensis stem bark on cadmium-induced oxidative damage in male albino rats’ liver was investigated. Male Wistar rats were divided into control, cadmium, and treatment groups. In the prophylactic experiment, Irvingia gabonensis (200 and 400 mg/kg body weight) was administered by oral gavage for 21 days before exposure to cadmium. Antioxidant marker enzymes such as reduced glutathione (GSH) levels, catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and lipid peroxidation (LPO) were determined in the liver and heart alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were monitored and histological examination was carried out. Results indicate that cadmium-induced rats had significantly increased relative weight of liver and heart when compared to controls. Treatment with Irvingia gabonensis at 200 and 400 mg/kg caused a significant decrease in relative weight of the organs. In cadmium-induced rats, serum ALT and AST activities and levels of LPO were increased whereas hepatic and cardiac marker enzymes significantly decreased. Furthermore, histological alteration in liver and aorta was observed in cadmium untreated rats and was ameliorated in cadmium rats treated with Irvingia gabonensis. In conclusion, the extract indicates antioxidant and hepatoprotective properties that eliminate the deleterious effects of toxic metabolites of cadmium.

Protective Effects of Parkia biglobosa Protein Isolate on Streptozotocin-Induced Hepatic Damage and Oxidative Stress in Diabetic Male Rats

This study sought to investigate the possible protective role of Parkia biglobosa seed protein isolate (PBPi) against streptozotocin-induced hepatic damage and oxidative stress in diabetic male rats. Prior to animal experiments, a HPLC fingerprint of PBPi was recorded. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight). Diabetic rats were orally treated daily with PBPi (200 or 400 mg/kg body weight) or insulin (5 U/kg, i.p.) for 28 days. The degree of protection was evaluated using biochemical parameters such as malondialdehyde (MDA) levels, serum transaminases (ALT and AST), total protein, total glutathione (Total GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and interleukin-6 (IL-6) activities. Histology of liver sections was also performed. The HPLC fingerprint of PBPi revealed eleven distinct peaks; PBPi at tested doses significantly attenuates STZ-induced elevated levels of serum IL-6, ALT and AST; and hepatic TBARS levels. Hepatic antioxidants (Total GSH, GST, SOD, CAT) as well as total protein were markedly restored in a dose-dependent manner. Histopathological results strongly support the protective role of PBPi. These results suggest PBPi could confer protection by ameliorating hepatic damage and oxidative stress caused by STZ in animal model possibly via its anti-inflammatory and antioxidant properties.

Chromatographic fingerprint analysis, antioxidant properties, and inhibition of cholinergic enzymes (acetylcholinesterase and butyrylcholinesterase) of phenolic extracts from Irvingia gabonensis (Aubry-Lecomte ex O’Rorke) Baill bark

Abstract Background: Irvingia gabonensis stem bark is a medicinal plant used in most parts of Africa to manage a number of ailments including neurodegenerative diseases that occur without scientific basis. This work characterized the phenolic composition, evaluated the cholinergic enzymes (acetylcholinesterase, AChE and butyrylcholinesterase, BChE) inhibition, and assessed the antioxidant activity of phenolic extracts from I. gabonensis (Aubry-Lecomte ex O‘Rorke) Baill bark. Methods: Total phenol and flavonoids content was evaluated in addition to antioxidant activity as shown by Fe2+ chelation, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability, and 2,2-azino-bis-(3-ethylbenthiazoline-6-sulfonic acid) (ABTS) radical scavenging ability. Inhibitory activities on AChE and BChE were evaluated. Results: The extract was found to be rich in phenolic acid (ellagic acid) and flavonoids (quercetrin, kaempferol, and apigenin). The phenolic extracts displayed DPPH radical scavenging ability (IC50=19.98 μg/mL), ABTS radical scavenging ability (IC50=18.25 μg/mL), iron chelation (IC50=113.10 μg/mL), and reducing power (Fe3+ to Fe2+) (5.94 mg ascorbic acid equivalent/100 g). Extracts of I. gabonensis inhibited AChE (IC50=32.90 μg/mL) and BChE (IC50=41.50 μg/mL) activities in concentration-dependent manner. Conclusions: Hence, possible mechanism through which the stem bark executes their anti-Alzheimer’s disease activity might be by inhibiting cholinesterase activities in addition to suppressing oxidative-stress-induced neurodegeneration.

Roles of Heat Shock Proteins in Apoptosis, Oxidative Stress, Human Inflammatory Diseases, and Cancer

Heat shock proteins (HSPs) play cytoprotective activities under pathological conditions through the initiation of protein folding, repair, refolding of misfolded peptides, and possible degradation of irreparable proteins. Excessive apoptosis, resulting from increased reactive oxygen species (ROS) cellular levels and subsequent amplified inflammatory reactions, is well known in the pathogenesis and progression of several human inflammatory diseases (HIDs) and cancer. Under normal physiological conditions, ROS levels and inflammatory reactions are kept in check for the cellular benefits of fighting off infectious agents through antioxidant mechanisms; however, this balance can be disrupted under pathological conditions, thus leading to oxidative stress and massive cellular destruction. Therefore, it becomes apparent that the interplay between oxidant-apoptosis-inflammation is critical in the dysfunction of the antioxidant system and, most importantly, in the progression of HIDs. Hence, there is a need to maintain careful balance between the oxidant-antioxidant inflammatory status in the human body. HSPs are known to modulate the effects of inflammation cascades leading to the endogenous generation of ROS and intrinsic apoptosis through inhibition of pro-inflammatory factors, thereby playing crucial roles in the pathogenesis of HIDs and cancer. We propose that careful induction of HSPs in HIDs and cancer, especially prior to inflammation, will provide good therapeutics in the management and treatment of HIDs and cancer.

HPLC-DAD fingerprinting analysis, antioxidant activities of Tithonia diversifolia (Hemsl.) A. Gray leaves and its inhibition of key enzymes linked to Alzheimer’s disease

Graphical abstract