Preclinical antidiabetic and antioxidant effects of Erythrophleum africanum (benth.) harms in streptozotocin-induced diabetic nephropathy.

OBJECTIVES: This study investigated the antidiabetic effects of the methanolic extract of E. africanum (MEEA) stem bark on streptozotocin (STZ)-induced diabetic nephropathy (DN) in Wistar rats. METHODS: The in vitro enzyme (α-amylase) inhibitory activity of MEEA was measured using a standard procedure. Diabetic rats with fasting blood glucose above 250 mg/dL were considered diabetic and were divided into the following groups: control (distilled water-treated), diabetic-control, diabetic metformin (100 mg/kg), diabetes + MEEA (150 mg/kg), and diabetes + MEEA (300 mg/kg) via oral gavage once daily for 14 days. At the end of the experimental period, kidney tissues were collected for biochemical and histological analyses. Kidney apoptosis and marker gene expression were measured by real-time quantitative PCR. RESULTS: MEEA exhibited α-amylase inhibitory effects. MEEA significantly (p<0.05) reduced the STZ-induced increases in blood glucose, serum urea, serum creatinine, uric acid, alanine aminotransferase, alkaline phosphatase, and malondialdehyde and increased the STZ-induced decreases in superoxide dismutase, catalase, and reduced glutathione. In addition, MEEA protects against DN by significantly downregulating the mRNA expression of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response binding protein (CREB), and cFOS and upregulating B-cell lymphoma 2 (Bcl-2), suggesting that the nephroprotective ability of MEEA is due to the modulation of the cAMP/PKA/CREB/cFOS signaling pathway. Furthermore, MEEA treatment protected against histopathological alterations observed in diabetic rats. CONCLUSIONS: The data from this study suggest that MEEA modulates glucose homeostasis and inhibits redox imbalance in DN rats.

Promising influences of zingerone against natural and chemical toxins: A comprehensive and mechanistic review.

Zingerone is a flavor phytochemical present in ginger, a flowering plant belonging to the Zingiberaceae family used as a condiment and herbal remedy. It possesses anti-inflammatory, antioxidant, and anti-apoptotic properties and also exhibits protective effects against radiation, chemicals, biological toxins, and oxidative stress. The current comprehensive literature review was performed in order to assess the therapeutical and protective properties of zingerone against various chemical and natural toxins by considering the mechanisms of action. Extensive searches were performed on Scopus, Web of Science, PubMed, and Google Scholar databases. Zingerone lessens oxidative stress, inflammation, apoptosis, and oxidative DNA damage by increasing the activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPX). It prevents alginate production, which increases the cell's susceptibility to macrophages, serum, and antibiotics and dramatically lowers the generation of proinflammatory cytokines brought on by lipopolysaccharide (LPS). Cytokine production, MAPK, and NF-κB activation are all inhibited dose-dependently by zingerone. Zingerone also reduces 8-OHdG over-expression in the liver tissue and the expression of NADPH oxidase 4 (NOX4), inflammatory cytokines (e.g., IFN-γ, IL-17, IL-6, COX-2, TNF-α, and iNOS mRNA level), decreases macrophage inflammatory protein cytokines and eliminates free radicals. It also suppresses matrix metalloproteinase-2 (MMP-2) and MMP-9 during tumor progression, showing its anti-angiogenic activity. Strong radioprotective properties of zingerone are demonstrated against radiation-induced toxicity. The authors hope this review gives researchers some insight into conducting novel clinical and preclinical studies on pharmaceutical applications and the efficiency of zingerone in cancer treatment, and drug adverse effects.

Syringic acid demonstrates an anti-inflammatory effect via modulation of the NF-κB-iNOS-COX-2 and JAK-STAT signaling pathways in methyl cellosolve-induced hepato-testicular inflammation in rats.

Syringic acid (SACI) is an emerging nutraceutical and antioxidant used in modern Chinese medicine. It has potential neuroprotective, anti-hyperglycemic, and anti-angiogenic properties. Methyl cellosolve (MCEL) has been reported to induce tissue inflammation in the testis, kidney, liver, and lung. This study aimed to investigate the effect and probable mechanism of action of SACI on MCEL-induced hepatic and testicular inflammation in male rats. Compared to the control group, administration of MCEL to rats significantly increased the levels of IL-6, TNF-α, iNOS, COX-2, and NF-κB in the liver and testis. Additionally, the total mRNA expressions of JAK1 (in the liver only), STAT1, and SOCS1 were significantly increased in both the liver and testis, while testicular JAK1 total mRNA levels were significantly decreased. The expression of PIAS1 protein was significantly higher in the liver and testis. Treatments with SACI at 25 (except liver iNOS), 50, and 75 mg/kg significantly decreased the levels of IL-6, TNF-α, iNOS, COX-2, and NF-κB compared to the control group. Furthermore, the total mRNA expressions of JAK1 and SOCS1 in the liver were significantly reduced by all doses of SACI investigated, while the total mRNA levels of liver and testis STAT1 were significantly reduced by 25 and 50 mg/kg of SACI only. In the testis, the mRNA level of SOCS1 was significantly reduced by all doses of SACI compared to MCEL only. Additionally, SACI (at 75 mg/kg) significantly reduced PIAS1 protein expression in the liver, while in the testis, SACI at all investigated doses significantly reduced the expression of PIAS1. In conclusion, SACI demonstrated a hepatic and testicular anti-inflammatory effect by inhibiting the MCEL-induced activation of the NF-κB and JAK-STAT signaling pathways in rats.

Aframomum melegueta secondary metabolites exhibit polypharmacology against SARS-CoV-2 drug targets: in vitro validation of furin inhibition.

COVID-19 pandemic is currently decimating the world's most advanced technologies and largest economies and making its way to the continent of Africa. Weak medical infrastructure and over-reliance on medical aids may eventually predict worse outcomes in Africa. To reverse this trend, Africa must re-evaluate the only area with strategic advantage; phytotherapy. One of the many plants with previous antiviral potency is against RNA viruses is Aframomum melegueta. In this study, one hundred (100) A. melegueta secondary metabolites have been mined and computational evaluated for inhibition of host furin, and SARS-COV-2 targets including 3C-like proteinase (Mpro /3CLpro ), 2'-O-ribose methyltransferase (nsp16) and surface glycoprotein/ACE2 receptor interface. Silica-gel column partitioning of A. melegueta fruit/seed resulted in 6 fractions tested against furin activity. Diarylheptanoid (Letestuianin A), phenylpropanoid (4-Cinnamoyl-3-hydroxy-spiro[furan-5,2'-(1'H)-indene]-1',2,3'(2'H,5H)-trione), flavonoids (Quercetin, Apigenin and Tectochrysin) have been identified as high-binding compounds to SARS-COV-2 targets in a polypharmacology manner. Di-ethyl-ether (IC50 = 0.03 mg/L), acetone (IC50 = 1.564 mg/L), ethyl-acetate (IC50 = 0.382 mg/L) and methanol (IC50 = 0.438 mg/L) fractions demonstrated the best inhibition in kinetic assay while DEF, ASF and MEF completely inhibited furin-recognition sequence containing Ebola virus-pre-glycoprotein. In conclusion, A. melegueta and its secondary metabolites have potential for addressing the therapeutic needs of African population during the COVID-19 pandemic.

Effect of Solanum macrocarpon Linn leaf aqueous extract on the brain of an alloxan-induced rat model of diabetes.

OBJECTIVE: This study was designed to evaluate the protective effect of aqueous extract of Solanum macrocarpon Linn leaf in the brain of an alloxan-induced rat model of diabetes. METHODS: The experimental model of diabetes was induced by a single intraperitoneal injection of freshly prepared alloxan. Rats were then divided into six groups: normal control, diabetes control, diabetes group treated with metformin, and three diabetes groups treated with different concentrations of S. macrocarpon. Rats were sacrificed on day 14 of the experiment and different brain biochemical parameters were assessed and compared between groups. RESULTS: Administration of different doses of S. macrocarpon leaf aqueous extract was associated with significantly reduced levels of fasting blood glucose, lipid peroxidation, neurotransmitters, cholinesterases, cyclooxygenase-2 and nitric oxide compared with diabetes control rats. In addition, antioxidant enzyme activities were significantly increased in diabetes rats administered 12.45, 24.9 and 49.8 mg/kg body weight of S. macrocarpon versus diabetes control rats. CONCLUSION: Aqueous extract of S. macrocarpon Linn leaf may be useful in the management of diabetic neuropathy.

Antihyperglycaemia and related gene expressions of aqueous extract of Gongronema latifolium leaf in alloxan-induced diabetic rats.

Context: Gongronema latifolium Benth (Asclepiadaceae) has been highly utilized in controlling diabetes mellitus traditionally in the eastern part of Nigeria. Objectives: Antihyperglycaemic and related gene expressions of aqueous extract of Gongronema latifolium leaf in alloxan-induced diabetic rats. Materials and methods: Forty-eight female Wistar rats were induced intraperitoneally using alloxan (150 mg/kg body weight). The rats were separated into six groups (n = 8) as follows: non-diabetic control, diabetic control, diabetic rats administered 5 mg/kg body weight of metformin, and diabetic rats administered 6.36, 12.72 and 25.44 mg/kg body weight (ethnobotanical doses) of G. latifolium orally daily. On the 14th day, the animals were sacrificed and different antihyperglycaemic parameters were evaluated as well as its related gene expressions. Results: Diabetic rats administered three doses of aqueous extract of G. latifolium significantly (p < 0.05) lowered the fasting blood glucose, glycated haemoglobin, serum lipid profiles, lipid peroxidation (5.62-1.2 µ/mg protein) levels, as well as gene expression of glucose-6-phosphatase in alloxan-induced diabetic rats. There was a significant (p < 0.05) increase in the liver glycogen content (16.23-112.5 mg glucose/2 g), antioxidant enzymes activities, glucose transporter (GLUT-2 and GLUT-4) levels and relative gene expression of hexokinase in diabetic rats administered different doses of aqueous extract of G. latifolium. Discussion and conclusions: It can be deduced that the aqueous extract of G. latifolium leaf at these doses may be useful in managing diabetes mellitus and its associated complications. Therefore, this extract may be a potent antidiabetic agent in clinical therapy in the future.

In vitro antioxidant activities and inhibitory effects of phenolic extract of Senecio biafrae (Oliv and Hiern) against key enzymes linked with type II diabetes mellitus and Alzheimer's disease.

The phenolic extract of Senecio biafrae leaves was investigated to determine the in vitro antioxidant, phenolic profiles, and inhibition of key enzymes relevant to type II diabetes mellitus (α-amylase and α-glucosidase) and Alzheimer's disease (acetylcholinesterase and butrylcholinesterase). The phenolic extract demonstrated significant scavenging abilities against all in vitro antioxidant parameters assessed. Reversed-phase HPLC of the extract revealed the presence of gallic acid, chlorogenic, caffeic acid, rutin, quercetin, and kaempferol. The extract also inhibited activities of α-amylase (IC 50 = 126.90 µg/ml), α-glucosidase (IC 50 = 139.66 µg/ml), acetylcholinesterase (IC 50 = 347.22 µg/ml), and butrylcholinesterase (IC 50 = 378.79 µg/ml), which may be attributed to the antioxidant potential of the extract and its phenolic composition. Therefore, this study suggests that the leaves of S. biafrae may be useful in the management of diabetes mellitus and Alzheimer's disease.

Anti-Hyperglycemic and Anti-Inflammatory Activities of Polyphenolic-Rich Extract of Syzygium cumini Linn Leaves in Alloxan-Induced Diabetic Rats.

In this study, anti-hyperglycemic and anti-inflammatory activities of polyphenolic-rich extract of Syzygium cumini leaves in alloxan-induced diabetic rats were determined. Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg body weight) in female Wistar rats. The rats were orally administered with 400 mg/kg free phenol, 400 mg/kg bound phenol, and 5 mg/kg metformin, respectively. On the 14th day of oral administration, the animals were sacrificed, anti-hyperglycemic and anti-inflammatory were assessed. Fasting blood glucose and glycated hemoglobin levels; homeostasis model assessment-insulin resistance scores, lipid peroxidation concentration, glucose-6-phosphatase activity, and all concentrations of anti-inflammatory studied in alloxan-induced diabetic rats were significantly ( P < .05) reduced with the administration of polyphenolic-rich extract of Syzygium cumini leaves. Also there was significant ( P < .05) increase in glycogen and insulin concentrations, pancreatic ß-cell scores, antioxidant enzymes and hexokinase activities, as well as glucose transporter levels in diabetic animals administered with polyphenolic-rich extract of S cumini leaves. The results indicate that S cumini leaves possess anti-hyperglycemic and anti-inflammatory activities.

Antihyperglycemic and antidyslipidemic activity of Musa paradisiaca-based diet in alloxan-induced diabetic rats.

This study was aimed at investigating the antihyperglycemic and antidyslipidemic activity of Musa paradisiaca-based diets in alloxan-induced diabetic mellitus rats. Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg b.w) in 48 randomly selected rats. The rats were randomly grouped into four as follows: normal rats fed Dioscorea rotundata-based diet, diabetic control rats fed D. rotundata-based diet, diabetic rats fed D. rotundata-based diet and administered metformin (14.2 mg/kg body weight) orally per day, and diabetic rats fed M. paradisiaca-based diet. Body weight and fasting blood glucose level were monitored, on 28th days the rats were sacrificed, liver was excised. Thereafter, the hyperglycemic and dyslipidemic statii of the induced diabetic animals were determined. The M. paradisiaca-based diet significantly (p < .05) reversed the levels of fasting blood glucose, with significant (p < .05) increase in insulin and glycogen concentrations. The diet also increased the activity of hexokinase with significant reduction (p < .05) in glucose-6-phosphatase and fructose-1-6-diphosphatase activities. M. paradisiaca-based diet demonstrated significant reduction (p < .05) in cholesterol, triacylglycerol (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and significant increase (p < .05) in high-density lipoprotein (HDL) compared with those of diabetic control group. Also, M. paradisiaca-based diet significantly (p < .05) reversed the activities of aspartate aminotransferase and alanine aminotransferase when compared with diabetic control animals. The consumption of this diet may be useful in ameliorating hyperglycemia and dyslipidemia in diabetes mellitus patients.

Ameliorative Activity of Ethanol Extract of Artocarpus heterophyllus Stem Bark on Pancreatic ß-Cell Dysfunction in Alloxan-Induced Diabetic Rats.

This study sought to investigate the ameliorative effects of ethanol extract Artocarpus heterophyllus (EAH) in alloxan-induced diabetic rats. The rats were divided into 6 groups, with groups 1 and 2 serving as nondiabetic and diabetic control, respectively; group 3 serving as diabetic rats treated with 5 mg/kg glibenclamide; and groups 4 to 6 were diabetic rats treated with 50, 100, and 150 mg/kg of EAH, respectively. Assays determined were serum insulin, lipid peroxidation, and antioxidant enzyme activities. EAH stem bark reduced fasting blood glucose and lipid peroxidation levels and increased serum insulin levels and activities of antioxidant enzymes. Data obtained demonstrated the ability of EAH stem bark to ameliorate pancreatic ß-cell dysfunction in alloxan-induced diabetic rats.