Unravelling the Influence of Chlorogenic Acid on the Antioxidant Phytochemistry of Avocado (Persea americana Mill.) Fruit Peel.

Oxidative stress is pivotal in the pathology of many diseases. This study investigated the antioxidant phytochemistry of avocado (Persea americana Mill.) peel. Different solvent extracts (dichloromethane, ethyl acetate, methanol, and water) of avocado peel were subjected to total phenol and flavonoid quantification, as well as in vitro radical scavenging and ferric reducing evaluation. The methanol extract was subjected to gradient column chromatographic fractionation. Fraction 8 (eluted with hexane:chloroform:methanol volume ratio of 3:6.5:0.5, respectively) was subjected to LC-MS analysis. It was assessed for cellular inhibition of lipid peroxidation and lipopolysaccharide (LPS)-induced ROS and NO production. The DPPH radical scavenging mechanism of chlorogenic acid was investigated using Density Functional Theory (DFT). The methanol extract and fraction 8 had the highest phenol content and radical scavenging activity. Chlorogenic acid (103.5 mg/mL) and 1-O-caffeoylquinic acid (102.3 mg/mL) were the most abundant phenolics in the fraction. Fraction 8 and chlorogenic acid dose-dependently inhibited in vitro (IC50 = 5.73 and 6.17 µg/mL) and cellular (IC50 = 15.9 and 9.34 µg/mL) FeSO4-induced lipid peroxidation, as well as LPS-induced ROS (IC50 = 39.6 and 28.2 µg/mL) and NO (IC50 = 63.5 and 107 µg/mL) production, while modulating antioxidant enzyme activity. The fraction and chlorogenic acid were not cytotoxic. DFT analysis suggest that an electron transfer, followed by proton transfer at carbons 3'OH and 4'OH positions may be the radical scavenging mechanism of chlorogenic acid. Considering this study is bioassay-guided, it is logical to conclude that chlorogenic acid strongly influences the antioxidant capacity of avocado fruit peel.

Ferulic acid interventions ameliorate NDEA-CCl4-induced hepatocellular carcinoma via Nrf2 and p53 upregulation and Akt/PKB-NF-κB-TNF-α pathway downregulation in male Wistar rats.

Hepatocellular carcinoma is a prevalent form of liver cancer that is life threatening. Many chemically synthesized anti-cancer drugs have various degrees of side effects. Hence, this study investigated the effect of FEAC interventions on NDEA-CCl4-induced HCAR in male Wistar rats. HCAR was induced by intraperitoneal administration of 200 mg/kg of NDEA and 0.5 mL/kg CCl4 (as a promoter of HCAR). Following the induction of HCAR, rats were treated differently with two different doses (25 and 50 mg/kg) of FEAC. HCAR induction was confirmed by the significant elevation of serum levels of ALT, AST, and α-FP. Also elevated significantly were liver levels of Akt/PKB, NF-κB, TNF-α, MDA, GSH, and activities of GST, SOD, and CAT, while levels of liver p53 and Nrf2 were significantly lowered compared with normal rats. Treatment interventions with both 25 and 50 mg/kg of FEAC against the DEN-CCl4-induced HCAR gave comparable effects, marked by a significant reduction in the levels of serum ALT, AST and α-FP, as well as liver levels of MDA, GSH, Akt/PKB, NF-κB, TNF-α, GST, SOD, and CAT, while levels of liver p53 and Nrf2 were significantly elevated compared with normal rats. Put together and judging by the outcomes of this study, FEAC being a potent antioxidant may also be potent against chemical-induced HCAR via upregulation of p53 and Nrf2, as well as downregulation of the Akt/PKB-NF-κB pathway in rats.

Reversal of mitochondrial permeability transition pore and pancreas degeneration by chloroform fraction of Ocimum gratissimum (L.) leaf extract in type 2 diabetic rat model.

Introduction: Unmanaged Diabetes Mellitus (DM) usually results to tissue wastage because of mitochondrial dysfunction. Adverse effects of some drugs used in the management of DM necessitates the search for alternative therapy from plant origin with less or no side effects. Ocimum gratissimum (L.) (OG) has been folklorically used in the management of DM. However, the mechanism used by this plant is not fully understood. This study was designed to investigate the effects of chloroform fraction of OG leaf (CFOG) in the reversal of tissue wastage in DM via inhibition of mitochondrial-mediated cell death in streptozotocin (STZ)-induced diabetic male Wistar rats. Methods: Air-dried OG leaves were extracted with methanol and partitioned successively between n-hexane, chloroform, ethylacetate and methanol to obtain their fractions while CFOG was further used because of its activity. Diabetes was induced in fifteen male Wistar rats, previously fed with high fat diet (28 days), via a single intraperitoneal administration of STZ (35 mg/kg). Diabetes was confirmed after 72 h. Another five fed rats were used as the normal control, treated with corn oil (group 1). The diabetic animals were grouped (n = 5) and treated for 28 days as follows: group 2 (diabetic control: DC) received corn oil (10 mL/kg), groups 3 and 4 were administered 400 mg/kg CFOG and 5 mg/kg glibenclamide, respectively. Body weight and Fasting Blood Glucose (FBG) were determined while Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and beta cell (HOMA-ß), and pancreatic tissue regenerating potential by CFOG were assessed. Activity-guided purification and characterization of the most active principle in CFOG was done using chromatographic and NMR techniques. The animals were sacrificed after 28 days, blood samples were collected and serum was obtained. Liver mitochondria were isolated and mitochondrial permeability transition (mPT) was investigated by spectrophotometry. Results: CFOG reversed diabetic-induced mPT pore opening, inhibited ATPase activity and lipid peroxidation. CFOG reduced HOMA-IR but enhanced HOMA-ß and caused regeneration of pancreatic cells relative to DC. Lupanol was a major metabolite of CFOG. Discussion: Normoglycemic effect of CFOG, coupled with reversal of mPT, reduced HOMA-IR and improved HOMA-ß showed the probable antidiabetic mechanism and tissue regenerating potentials of OG.

The protective roles of citrus flavonoids, naringenin, and naringin on endothelial cell dysfunction in diseases.

The endothelial cells (ECs) make up the inner lining of blood vessels, acting as a barrier separating the blood and the tissues in several organs. ECs maintain endothelium integrity by controlling the constriction and relaxation of the vasculature, blood fluidity, adhesion, and migration. These actions of ECs are efficiently coordinated via an intricate signaling network connecting receptors, and a wide range of cellular macromolecules. ECs are naturally quiescent i.e.; they are not stimulated and do not proliferate. Upon infection or disease, ECs become activated, and this alteration is pivotal in the pathogenesis of a spectrum of human neurological, cardiovascular, diabetic, cancerous, and viral diseases. Considering the central position that ECs play in disease pathogenesis, therapeutic options have been targeted at improving ECs integrity, assembly, functioning, and health. The dietary intake of flavonoids present in citrus fruits has been associated with a reduced risk of endothelium dysfunction. Naringenin (NGN) and Naringin (NAR), major flavonoids in grapefruit, tomatoes, and oranges possess anti-inflammatory, antioxidant properties, and cell survival potentials, which improve the health of the vascular endothelium. In this review, we provide a comprehensive summary and present the advances in understanding of the mechanisms through which NGN and NAR modulate the biomarkers of vascular dysfunction and protect the endothelium against unresolved inflammation, oxidative stress, atherosclerosis, and angiogenesis. We also provide perspectives and suggest further studies that will help assess the efficacy of citrus flavonoids in the therapeutics of human vascular diseases.

Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches.

Prostate cancer is one of the malignancies that affects men and significantly contributes to increased mortality rates in men globally. Patients affected with prostate cancer present with either a localized or advanced disease. In this review, we aim to provide a holistic overview of prostate cancer, including the diagnosis of the disease, mutations leading to the onset and progression of the disease, and treatment options. Prostate cancer diagnoses include a digital rectal examination, prostate-specific antigen analysis, and prostate biopsies. Mutations in certain genes are linked to the onset, progression, and metastasis of the cancer. Treatment for localized prostate cancer encompasses active surveillance, ablative radiotherapy, and radical prostatectomy. Men who relapse or present metastatic prostate cancer receive androgen deprivation therapy (ADT), salvage radiotherapy, and chemotherapy. Currently, available treatment options are more effective when used as combination therapy; however, despite available treatment options, prostate cancer remains to be incurable. There has been ongoing research on finding and identifying other treatment approaches such as the use of traditional medicine, the application of nanotechnologies, and gene therapy to combat prostate cancer, drug resistance, as well as to reduce the adverse effects that come with current treatment options. In this article, we summarize the genes involved in prostate cancer, available treatment options, and current research on alternative treatment options.

Reno-Hepatoprotective and Antidiabetic Properties of Methanol Leaf Extract of Laportea Aestuans in Wistar Rats.

Toxicities due to exposure to arsenic-contaminated water and the occurrence of diabetes mellitus are major health concerns. Treatment of these concerns using therapeutic measures have recorded limited success. Traditionally, Laportea aestuans (LA) has been used in managing various diseases. Hence, we investigated the reno-hepatoprotective/antidiabetic potentials of methanol leaf extract of LA (MeLELA) in male Wistar rats. Thirty rats (100-150 g) were equally distributed into 6 groups: Group I (vehicle-treated); group II received 2.5 mg/kg sodium arsenite (SA) thrice a week for 2 weeks; group III received streptozotocin (STZ, 50 mg/kg once); group IV received 200 mg/kg LA daily for 14 days; group V received SA and LA; group VI received STZ and LA. Sodium arsenite and STZ induced reno-hepatotoxicity and diabetes, respectively. Phytochemical screening, biomarkers/enzyme activities, blood glucose levels, micronucleus assay, kidney, liver and pancreas histologies were determined according to standard procedures. Alkaloids, carotenoids and flavonoids were present in abundance. Both SA-and STZ-treated groups recorded significant (p < 0.05) reductions in serum protein concentrations, while co-treatment with LA significantly restored the levels. The SA-induced significant increase in creatinine/urea levels were significantly reduced by LA. Co-treatment of each of SA-and STZ-treated groups, respectively, with LA significantly decreased the elevated serum alanine and aspartate aminotransferases' activities. Increased blood glucose level in diabetic group was remarkably lowered by LA. Also, the SA-induced frequency of micronucleated polychromatic erythrocytes was significantly ameliorated by LA. Conclusively, LA is protective against SA-induced toxicity and STZ-induced diabetes in Wistar rats.

A Common Insecticide Induced-Oxidative Stress in Wistar Rats: Significance for Humans and Implications for Nutritional Modulation of Insecticide Toxicity.

OBJECTIVE: This study examined the levels of selected micronutrients and associated biochemical changes in rats exposed to Baygon® insecticide. Arsenic is a toxic metalloid commonly used in insecticides manufacture but unheralded. METHODS: Fifteen rats, divided into three equal groups: Group I (control); group II (administered 2.5 mg/kg sodium arsenite (SA) on alternate days for four weeks); group III (exposed to 14.0 mL Baygon® m-3 cage volume daily for four weeks). Serum levels of arsenic (As), selenium (Se) and zinc (Zn) were determined using flame atomic absorption spectrophotometry (FAAS). Reduced glutathione (GSH), glutathione peroxidase (GPx), and total protein (TP) were determined spectrophotometrically. RESULTS: Arsenic and Se levels were significantly raised in groups II and III compared with control (p < 0.05), unlike Zn levels that were significantly decreased in groups II and III (p < 0.05) in both. No significant change in the activity of GPx; though the activity increased in the group treated with SA, but decreased in the group treated with Baygon® compared to control (P < 0.05). Histology of the liver and lung was unaltered in control, but in contrast, the SA-treated group demonstrated moderate fibrous hyperplasia with prominent highly infiltrated portal area in the liver; while the lung revealed thickened alveolar walls from proliferated pneumocytes. In the Baygon®-treated group, there was mild hyperplasia of the fibrous connective tissue and congested prominent portal areas; while the lung exhibited severe thickened alveolar walls due to proliferated pneumocytes. CONCLUSION: Exposure of rats to Baygon® elicited alteration of key trace elements involved in the antioxidant system, culminating in oxidative stress with attendant deleterious effects. One significance of this for humans is that it has great potentials for possible nutritional modulation of insecticide toxicity with micronutrients, especially with zinc, holding great promise in tropical developing countries.

Hepato-Genoprotective Activities of Methanol Extract of The Stem Bark of Adansonia Digitata LINN. In Wistar Rats Challenged with Sodium Arsenite.

Arsenic exposure is an issue of concern in developing countries, consequently leading to arsenicosis which has been implicated in the development of cancers. The stem bark of Adansonia digitata (SBAD) has many traditional medicinal uses. The aim of the present study was to assess the antigenotoxic and hepatoprotective effects of methanol extract of SBAD (MESBAD) against sodium arsenite - induced toxicities in Wistar rats. These were assessed using the micronucleus induction assay and liver function tests with histology respectively. Thirty (30) rats distributed into six groups of five animals each were used for the experiment. Negative control (distilled water and rat pellets only), positive control [2.5 mg/kg body weight of sodium arsenite (SA)]. Test animals were challenged with SA and treated with 300 or 400 mg/kg body weight of MESBAD. The phytochemical analysis was also carried out according to standard procedures. The SA significantly (p<0.05) increased the activities of aspartate aminotransferace (AST) and the number of micronucleated polychromatic erythrocytes (nMPCEs) induced in the bone marrow as compared with the negative control. Treatment with MESBAD significantly (p<0.05) reduced the activities of AST and nMPCEs induced, histopatological examination of the liver showed that MESBAD reduced the severe portal and central venous congestion induced by SA, phytochemical analysis showed that MESBAD possess high concentration of alkaloids, saponins, flavonoids and total polyphenols. Methanol extract of the stem bark of Adansonia digitata mitigates SA-induced toxicities probably through radical scavenging activities.

Methanol Extract of Adansonia digitata Leaf Protects Against Sodium Arsenite-induced Toxicities in Male Wistar Rats.

BACKGROUND: Human and animal population exposure to arsenic through the consumption of arsenic contaminated water is rampant in many parts of the world. Protective agents of medicinal plants origin could provide maximum protection against toxicities of various kinds. OBJECTIVE: The protective role of orally administered methanol extract of the leaves of Adansonia digitata (MELAD) on sodium arsenite (SA) - induced clastogenicity and hepatotoxicity in male Wistar rats was evaluated. MATERIALS AND METHODS: Thirty male Wistar rats divided into six Groups (1-6) of five animals each were used for the study. Group 1 (negative control) received distilled water and normal diet only, Groups 2-6 received the extract (at 250 or 500 mg/kg body weight) and/or SA at 2.5 mg/kg body weight. RESULTS: There was statistically significant (P < 0.05) increase in the number of micronucleated polychromatic erythrocytes and lipid peroxidation in the SA group as compared with the negative control and treated groups. Administration of the extract reduced the effects of SA on the above parameters. Activities of serum alanine and aspartate aminotransferases did not show statistically significant effects; however, the histological analyses revealed periportal cellular infiltration by mononuclear cells, whereas the MELAD treated groups show mild cellular infiltration and mild portal congestion. CONCLUSIONS: MELAD protect against SA-induced toxicities in rats, and it may offer protection in circumstances of co-exposure and cases of arsenicosis. SUMMARY: MELAD extract significantly reduce the lipid peroxidation induced by sodium arsenite in the liver of rats.MELAD did not show profound effects on the activities of serum alanine (ALT) and aspartate (AST) aminotranferases.MELAD offered significant protection against sodium arsenite-induced genotoxicity in the micronuclei induction assay.In the circumstances of co-exposure to arsenic contamination, MELAD may protect against sodium arsenite-induced toxicities. Abbreviations Used: MELAD: Methanol extract of the leaves of Adansonia digitata, SA: Sodium arsenite, nMPCEs: Number of micronucleated polychromatic erythocytes; ALT: Alanine aminotranferase; AST: Aspartate aminotranferase, TBARS: Thiobarbituric acid reactive substances, TBA: Thiobarbituric acid, MDA: malondialdehyde, Sodium arsenite (NaAsO2), IARC: International Agency for Research on Cancer.

Modulatory role of Acacia honey from north-west Nigeria on sodium arsenite-induced clastogenicity and oxidative stress in male Wistar rats.

Effect of Acacia honey from north-west Nigeria on sodium arsenite-induced oxidative damage and clastogenicity in male Wistar rats was investigated. Animals were divided into four groups and were treated daily via oral gavage for one week before they were sacrificed. Brain, liver and blood serum were collected for antioxidant and protein assays. Clastogenicity, in vitro antioxidant activity, vitamins and minerals were also evaluated. From the results, co-administration of Acacia honey with sodium arsenite on the animals increased (P < 0.05) glutathione peroxidase, superoxide dismutase and catalase activities with concomitant decrease in malondialdehyde levels and anti-clastogenic effects relative to the group treated with sodium arsenite only. The honey possesses reducing power, high hydrogen peroxide scavenging activity, good amount of vitamins (A, C and E), flavonoids (5.08 ± 0.92 mg QE/100 g) and phenolics (5.40 ± 0.69 mg GAE/100 g). The minerals present include zinc, iron, sodium, magnesium, potassium and calcium. In conclusion, Acacia honey from Nigeria may mitigate oxidative stress and clastogenicity.

Toxicity associated with repeated administration of artemether-lumefantrine in rats.

Chemotherapy remains an important approach in the fight against malaria. Artemether-lumefantrine combination is widely in use due to its effectiveness against Plasmodium falciparum. Misuse in the form of multiple repeated doses of this anti-malaria drug is rampant in Nigeria. This study was designed to assess the hepatotoxic and clastogenic potential of extreme misuse of artemether-lumefantrine in rats. Graded doses of artemether-lumefantrine (1-5 mg/kg body weight) were administered by oral gavage for 6 weeks, twice daily, for 3 consecutive days per week. Artemether-lumefantrine, at all doses, did not have significant effects on the body and relative liver weight of treated group compared to the negative control group. The mean γ-glutamyltransferase, alanine, and aspartate aminotransaminase activity in groups of artemether-lumefantrine treated rats were significantly higher (p < 0.05) than that of the negative control group indicating that repeated administration of artemether-lumefantrine may be hepatotoxic. Findings from histological analyses of liver cross-section support the enzyme pattern of hepatoxicity. In addition, the drug, at all experimental doses, significantly induced (p < 0.05) formation of micronucleated polychromatic erythrocytes in the bone marrow cells of the treated rats compared with the negative control indicating clastogenic potential of the drug when misused.