Impact of coffee and its bioactive compounds on the risks of type 2 diabetes and its complications: A comprehensive review.

BACKGROUND: Coffee beans have a long history of use as traditional medicine by various indigenous people. Recent focus has been given to the health benefits of coffee beans and its bioactive compounds. Research on the bioactivities, applications, and effects of processing methods on coffee beans' phytochemical composition and activities has been conducted extensively. The current review attempts to provide an update on the biological effects of coffee on type 2 diabetes (T2D) and its comorbidities. METHODS: Comprehensive literature search was carried out on peer-reviewed published data on biological activities of coffee on in vitro, in vivo and epidemiological research results published from January 2015 to December 2022, using online databases such as PubMed, Google Scholar and ScienceDirect for our searches. RESULTS: The main findings were: firstly, coffee may contribute to the prevention of oxidative stress and T2D-related illnesses such as cardiovascular disease, retinopathy, obesity, and metabolic syndrome; secondly, consuming up to 400 mg/day (1-4 cups per day) of coffee is associated with lower risks of T2D; thirdly, caffeine consumed between 0.5 and 4 h before a meal may inhibit acute metabolic rate; and finally, both caffeinated and decaffeinated coffee are associated with reducing the risks of T2D. CONCLUSION: Available evidence indicates that long-term consumption of coffee is associated with decreased risk of T2D and its complications as well as decreased body weight. This has been attributed to the consumption of coffee with the abundance of bioactive chemicals.

Croton gratissimus Burch Herbal Tea Exhibits Anti-Hyperglycemic and Anti-Lipidemic Properties via Inhibition of Glycation and Digestive Enzyme Activities.

Over the years, the world has continued to be plagued by type 2 diabetes (T2D). As a lifestyle disease, obese individuals are at higher risk of developing the disease. Medicinal plants have increasingly been utilized as remedial agents for managing metabolic syndrome. The aim of the present study was to investigate the in vitro anti-hyperglycemic and anti-lipidemic potential of Croton gratissimus herbal tea infusion. The inhibitory activities of C. gratissimus on carbohydrate (α-glucosidase and α-amylase) and lipid (pancreatic lipase) hydrolyzing enzymes were determined, and the mode of inhibition of the carbohydrate digestive enzymes was analyzed and calculated via Lineweaver-Burk plots and Michaelis Menten's equation. Its effect on Advanced Glycation End Product (AGE) formation, glucose adsorption, and yeast glucose utilization were also determined. High-performance liquid chromatography (HPLC) was used to quantify the possible phenolic compounds present in the herbal tea infusion, and the compounds were docked with the digestive enzymes. C. gratissimus significantly (p < 0.05) inhibited α-glucosidase (IC50 = 60.56 ± 2.78 µg/mL), α-amylase (IC50 = 35.67 ± 0.07 µg/mL), as well as pancreatic lipase (IC50 = 50.27 ± 1.51 µg/mL) in a dose-dependent (15-240 µg/mL) trend. The infusion also inhibited the non-enzymatic glycation process, adsorbed glucose effectively, and enhanced glucose uptake in yeast cell solutions at increasing concentrations. Molecular docking analysis showed strong binding affinity between HPLC-quantified compounds (quercetin, caffeic acid, gallic acid, and catechin) of C. gratissimus herbal tea and the studied digestive enzymes. Moreover, the herbal tea product did not present cytotoxicity on 3T3-L1 cell lines. Results from this study suggest that C. gratissimus herbal tea could improve glucose homeostasis and support its local usage as a potential anti-hyperglycemic and anti-obesogenic agent. Further in vivo and molecular studies are required to bolster the results from this study.

Phytochemical Properties of Croton gratissimus Burch (Lavender Croton) Herbal Tea and Its Protective Effect against Iron-Induced Oxidative Hepatic Injury.

Oxidative stress plays a vital role in the pathogenesis and progression of various liver diseases. Traditional medicinal herbs have been used worldwide for the treatment of chronic liver diseases due to their high phytochemical constituents. The present study investigated the phytochemical properties of Croton gratissimus (lavender croton) leaf herbal tea and its hepatoprotective effect on oxidative injury in Chang liver cells, using an in vitro and in silico approach. C. gratissimus herbal infusion was screened for total phenolic and total flavonoid contents as well as in vitro antioxidant capacity using ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picryl-hydrazyl (DPPH) methods. Oxidative hepatic injury was induced by incubating 0.007 M FeSO4 with Chang liver cells which has been initially incubated with or without different concentrations (15-240 µg/mL) of C. gratissimus infusion or the standard antioxidants (Gallic acid and ascorbic acid). C. gratissimus displayed significantly high scavenging activity and ferric reducing capacity following DPPH and FRAP assays, respectively. It had no cytotoxic effect on Chang liver cells. C. gratissimus also significantly elevated the level of hepatic reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activities as well as suppressed the malondialdehyde (MDA) level in oxidative hepatic injury. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis of the herbal tea revealed the presence of 8-prenylnaringenin, flavonol 3-O-D-galactoside, caffeine, spirasine I, hypericin, pheophorbide-a, and 4-methylumbelliferone glucuronide. In silico oral toxicity prediction of the identified phytochemicals revealed no potential hepatotoxicity. Molecular docking revealed potent molecular interactions of the phytochemicals with SOD and catalase. The results suggest the hepatoprotective and antioxidative potentials of C. gratissimus herbal tea against oxidative hepatic injury.

Lippia javanica (Burm. F.) Herbal Tea: Modulation of Hepatoprotective Effects in Chang Liver Cells via Mitigation of Redox Imbalance and Modulation of Perturbed Metabolic Activities.

Introduction: Hepatic oxidative injury is one of the pathological mechanisms that significantly contributes to the development of several liver diseases. In the present study, the hepatoprotective effect of Lippia javanica herbal tea was investigated in Fe2+- mediated hepatic oxidative injury. Methods: Using an in vitro experimental approach, hepatic oxidative injury was induced by co-incubating 7 mM FeSO4 with Chang liver cells that have been pre-incubated with or without different concentrations (15-240 µg/mL) of L. javanica infusion. Gallic acid and ascorbic acid served as the standard antioxidants. Results: The infusion displayed a reducing antioxidant activity in ferric-reducing antioxidant power (FRAP) assay and a potent scavenging activity on 2,2-diphenyl-2- picrylhydrazyl (DPPH) radical. Pretreatment with L. javanica infusion significantly elevated the levels of reduced glutathione and non-protein thiol, and the activities of superoxide dismutase (SOD) and catalase, with concomitant decrease in hepatic malondialdehyde levels, acetylcholinesterase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase and lipase activities. The infusion showed the presence of phytoconstituents such as phenolic compounds, tannins, phenolic glycosides and terpenoids when subjected to liquid chromatography-mass spectrometry analysis. Molecular docking revealed a strong binding affinity of dihydroroseoside and obacunone with both SOD and catalase compared to other phytoconstituents. Conclusion: These results portray a potent antioxidant and hepatoprotective effect of L. javanica, which may support the local usage of the herbal tea as a prospective therapeutic agent for oxidative stress-related liver diseases.

Cannabis sativa L. modulates altered metabolic pathways involved in key metabolisms in human breast cancer (MCF-7) cells: A metabolomics study.

The present study investigated the ability of Cannabis sativa leaves infusion (CSI) to modulate major metabolisms implicated in cancer cells survival, as well as to induce cell death in human breast cancer (MCF-7) cells. MCF-7 cell lines were treated with CSI for 48 h, doxorubicin served as the standard anticancer drug, while untreated MCF-7 cells served as the control. CSI caused 21.2% inhibition of cell growth at the highest dose. Liquid chromatography-mass spectroscopy (LC-MS) profiling of the control cells revealed the presence of carbohydrate, vitamins, oxidative, lipids, nucleotides, and amino acids metabolites. Treatment with CSI caused a 91% depletion of these metabolites, while concomitantly generating selenomethionine, l-cystine, deoxyadenosine triphosphate, cyclic AMP, selenocystathionine, inosine triphosphate, adenosine phosphosulfate, 5'-methylthioadenosine, uric acid, malonic semialdehyde, 2-methylguanosine, ganglioside GD2 and malonic acid. Metabolomics analysis via pathway enrichment of the metabolites revealed the activation of key metabolic pathways relevant to glucose, lipid, amino acid, vitamin, and nucleotide metabolisms. CSI caused a total inactivation of glucose, vitamin, and nucleotide metabolisms, while inactivating key lipid and amino acid metabolic pathways linked to cancer cell survival. Flow cytometry analysis revealed an induction of apoptosis and necrosis in MCF-7 cells treated with CSI. High-performance liquid chromatography (HPLC) analysis of CSI revealed the presence of cannabidiol, rutin, cinnamic acid, and ferulic. These results portray the antiproliferative potentials of CSI as an alternative therapy for the treatment and management of breast cancer as depicted by its modulation of glucose, lipid, amino acid, vitamin, and nucleotide metabolisms, while concomitantly inducing cell death in MCF-7 cells.

Kolaviron modulates dysregulated metabolism in oxidative pancreatic injury and inhibits intestinal glucose absorption with concomitant stimulation of muscle glucose uptake.

This present study investigated the antioxidative and antidiabetic properties of kolaviron by analysing its inhibitory effect on key metabolic activities linked to T2D, in vitro and ex vivo. Kolaviron significantly inhibited α-glucosidase and α-amylase activities, and intestinal glucose absorption dose-dependently, while promoting muscle glucose uptake. Induction of oxidative pancreatic injury significantly depleted glutathione level, superoxide dismutase, catalase, and ATPase activities, while elevating malondialdehyde and nitric oxide levels, acetylcholinesterase and chymotrypsin activities. These levels and activities were significantly reversed in tissues treated with kolaviron. Kolaviron depleted oxidative-induced metabolites, with concomitant restoration of oxidative-depleted metabolites. It also inactivated oxidative-induced ascorbate and aldarate metabolism, pentose and glucuronate interconversions, fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, and arginine and proline metabolism, while reactivating selenocompound metabolism. These results depict the antidiabetic properties of kolaviron as indicated by its ability to attenuate oxidative-induced enzyme activities and dysregulated metabolisms, and modulated the enzyme activities linked to hyperglycaemia.

Ferulic acid mitigates diabetic cardiomyopathy via modulation of metabolic abnormalities in cardiac tissues of diabetic rats.

Cardiovascular abnormalities have been reported as a major contributor of diabetic mortality. The protective effect of ferulic acid on diabetic cardiomyopathy in fructose-streptozotocin induced type 2 diabetes (T2D) rat model was elucidated in this study. Type 2 diabetic rats were treated by oral administration of low (150 mg/kg b.w) and high (300 mg/kg b.w) doses of ferulic acid. Metformin was used as the antidiabetic drug. Rats were humanely euthanized after 5 weeks of treatment, and their blood and hearts were collected. Induction of T2D depleted the levels of reduced glutathione, glycogen, and HDL-cholesterol and the activities of superoxide dismutase, catalase, ENTPDase, and 5'nucleotidase. It simultaneously triggered increase in the levels of malondialdehyde, total cholesterol, triglyceride, LDL-cholesterol, creatinine kinase-MB as well as activities of acetylcholinesterase, angiotensin converting enzyme (ACE), ATPase, glucose-6-phopsphatase, fructose-1,6-bisphophatase, glycogen phosphorylase, and lipase. T2D induction further revealed an obvious degeneration of cardiac muscle morphology. However, treatment with ferulic acid markedly reversed the levels and activities of these biomarkers with concomitant improvement in myocardium structural morphology, which had favorable comparison with the standard drug, metformin. Additionally, T2D induction led to the depletion of 40%, 75%, and 33% of fatty acids, fatty esters, and steroids, respectively, with concomitant generation of eicosenoic acid, gamolenic acid, and vitamin E. Ferulic acid treatment restored eicosanoic acid, 2-hydroxyethyl ester, with concomitant generation of 6-octadecenoic acid, (Z)-, cis-11-eicosenoic acid, tridecanedioic acid, octadecanoic acid, 2-hydroxyethyl ester, ethyl 3-hydroxytridecanoate, dipalmitin, cholesterol isocaproate, cholest-5-ene, 3-(1-oxobuthoxy)-, cholesta-3,5-diene. These results suggest the cardioprotective potential of ferulic acid against diabetic cardiomyopathy.

Ferulic acid improves glucose homeostasis by modulation of key diabetogenic activities and restoration of pancreatic architecture in diabetic rats.

There are increasing concerns on the rising cases of diabetes mellitus with type 2 diabetes (T2D) being of major interest as well as the cost of its treatment. Plant phenolic compounds are natural and potent antioxidants that have been widely reported for their antidiabetic activities properties, one of which is ferulic acid. The effect of ferulic acid (FA) on major diabetogenic activities and pancreatic architecture linked to T2D was investigated in T2D rats. T2D was induced in male Sprague-Dawley rats using the fructose-streptozotocin model. Diabetic rats were treated with FA at 150 or 300 mg/kg bodyweight (bw). Normal control consisted of rats administered with food and water, while diabetic control consisted of untreated diabetic rats. Metformin was used as the standard drug. The rats were humanely sacrificed after 5 weeks of treatment. Their blood, liver, and pancreas were collected for analysis. Total glycogen content and carbohydrate metabolic enzymes activities were analyzed in the liver, while the pancreas and serum from blood were analyzed for oxidative stress biomarkers, purinergic and cholinergic enzyme activities, and amylase and lipase activities. The pancreatic tissue was further subjected to microscopic and histological examinations. FA caused a significant (p < 0.05) decrease in blood glucose level, with concomitant increase in serum insulin level. Treatment with FA also led to elevated levels of GSH, HDL-c, SOD, and catalase activities, while concomitantly suppressing malondialdehyde, cholesterol, triglyceride, LDL-c, NO, ALT, AST, creatinine, urea, and uric acid levels, acetylcholinesterase, ATPase, ENTPDase, 5'-nucleotidase, lipase, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-biphosphatase activities. Histology analysis revealed an intact pancreatic morphology in FA-treated diabetic rats. While transmission electron microscopy (TEM) analysis revealed an intact pancreatic ultrastructure and increased number of insulin granules in ß-cells. Taken together, these results portray that the antidiabetic potentials of ferulic acid involves modulation of major diabetogenic activities and maintenance of the pancreatic ultrastructure architecture.

Senna petersiana (Bolle) leaf extract modulates glycemic homeostasis and improves dysregulated enzyme activities in fructose-fed streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Senna petersiana (Bolle) is a native South African medicinal shrub combined locally with other plant products to manage diabetes or used as a single therapy for several other ailing conditions. AIM OF THE STUDY: This study evaluated the antidiabetic and antilipidemic effects of S. petersiana leaf ethanol extract and its modulatory effects on dysregulated enzyme activities in fructose-fed streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Six groups of 6-weeks old male Sprague Dawley rats were used in this study. Diabetes was induced in four of the groups by injecting (i.p.) 40 mg/kg of streptozotocin after a two-weeks feeding of 10% fructose via drinking water, while animals in the two normal groups were given similar volume of vehicle buffer and normal drinking water, respectively. After the confirmation of diabetes, treatment with 150 and 300 mg/kg body weight of the ethanolic leaf extract of S. petersiana proceeded for a period of 6 weeks. RESULTS: Oral administration of S. petersiana leaf extract significantly lowered blood glucose, food and liquid intake, glycosylhaemoglobin in blood, liver and cardiac biomarkers, and lipid profile in serum and atherogenic index (AIP) in both the low and high-dose treated animal groups. This was accompanied by a simultaneous increase in Homeostatic Model Assessment-beta (HOMA-ß) score, serum high-density lipoproteins cholesterol (HDL-c), and insulin levels. It also improved pancreatic and serum-reduced glutathione (GSH) levels, catalase, and superoxide dismutase (SOD) enzymes activities with a simultaneous reduction in malondialdehyde (MDA) and nitric oxide (NO) concentrations. Moreover, the extract modulated dysregulated α-amylase, lipase, cholinesterase, and 5' nucleotidase enzyme activities in pancreatic tissue as well as glycogen metabolism in the liver. Analysis of the phytochemicals in the S. petersiana extract showed the presence of phytol, 4a,7,7,10a-tetramethyldodecahydrobenzo[f]-chromen-3-ol, phytol acetate, solasodine glucoside, cassine, veratramine and solasodine acetate. Amongst these compounds, solasodine glucoside had the best binding energy (ΔG) with the selected diabetes-linked enzymes via molecular docking simulation. CONCLUSION: Data from this study demonstrate the antidiabetic effects of S. petersiana leaf extract via the modulation of the dysregulated indices involved in type 2 diabetes and its associated complications. Although it has been shown safe in animals, further toxicological studies are required to ensure its safety for diabetes management in humans.

Hibiscus sabdariffa L. polyphenolic-rich extract promotes muscle glucose uptake and inhibits intestinal glucose absorption with concomitant amelioration of Fe2+ -induced hepatic oxidative injury.

In this current study, the antidiabetic effectiveness of Hibiscus sabdariffa and its protective function against Fe2+ -induced oxidative hepatic injury were elucidated using in vitro, in silico, and ex vivo studies. The oxidative damage was induced in hepatic tissue by incubation with 0.1 mMolar ferrous sulfate (FeSO4) and then treated with different concentrations of crude extracts (ethyl acetate, ethanol, and aqueous) of H. sabdariffa flowers for 30 min at 37°C. When compared to ethyl acetate and aqueous extracts, the ethanolic extract displayed the most potent scavenging activity in ferric-reducing antioxidant power (FRAP), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and nitric oxide (NO) assays, with IC50 values of 2.8 µl/ml, 3.3 µl/ml, and 9.2 µl/ml, respectively. The extracts significantly suppressed α-glucosidase and α-amylase activities (p < .05), with the ethanolic extract demonstrating the highest activity. H. sabdariffa significantly (p < .05) raised reduced glutathione (GSH) levels while simultaneously decreasing malondihaldehyde (MDA) and NO levels and increasing superoxide dismutase (SOD) and catalase activity in Fe2+ induced oxidative hepatic injury. The extract of the plant inhibited intestinal glucose absorption and increased muscular glucose uptake. The extract revealed the presence of several phenolic compounds when submitted to gas chromatography-mass Spectroscopy (GC-MS) screening, which was docked with α-glucosidase and α- amylase. The molecular docking displayed the compound 4-(3,5-Di-tert-butyl-4-hydroxyphenyl)butyl acrylate strongly interacted with α-glucosidase and α-amylase and had the lowest free binding energy compared to other compounds and acarbose. These results suggest that H. sabdariffa has promising antioxidant and antidiabetic activity. PRACTICAL APPLICATIONS: In recent years, there has been increased concern about the side effects of synthetic anti-diabetic drugs, as well as their expensive cost, especially in impoverished nations. This has instigated a radical shift towards the use of traditional plants, which are rich in phytochemicals many years ago. Among these plants, H. sabdariffa has been used to treat diabetes in traditional medicine. In this present study, H. sabdariffa extracts demonstrated the ability to inhibit carbohydrate digesting enzymes, facilitate muscle glucose uptake and attenuate oxidative stress in oxidative hepatic injury. Hence, demonstrating H. sabdariffa's potential to protect against oxidative damage and the complications associated with diabetes. Consumption of Hibiscus tea or juice may be a potential source for developing an anti-diabetic drug.

Caffeic acid regulates glucose homeostasis and inhibits purinergic and cholinergic activities while abating oxidative stress and dyslipidaemia in fructose-streptozotocin-induced diabetic rats.

OBJECTIVES: The antidiabetic potential of caffeic acid in fructose/streptozotocin-induced type 2 diabetic rats was examined in this study. METHODS: Male Sprague-Dawley rats were supplied with 10% fructose solution for 14 days followed by an intraperitoneal injection of 40 mg/kg bw streptozotocin to induce type 2 diabetes (T2D). Rats were treated with both low (150 mg/kg bw) and high (300 mg/kg bw) doses of caffeic acid for 5 weeks, while the positive control group was treated with metformin (200 mg/kg bw). KEY FINDINGS: Treatment with caffeic acid significantly decreased blood glucose levels and elevated serum insulin levels while improving glucose tolerance, pancreatic ß-cell function and morphology. It also led to a significant reduction of serum cholesterol, triglyceride, LDL-cholesterol, ALT, AST, creatinine, urea and uric acid levels, while increasing HDL cholesterol levels. Caffeic acid significantly (P < 0.05) elevated hepatic glycogen level, serum and pancreatic glutathione level, superoxide dismutase and catalase activities with a concomitant decrease in malondialdehyde level, α-amylase, lipase, adenosine triphosphatase (ATPase), ectonucleoside triphosphate diphosphohydrolase (ENTPDase), 5'-nucleotidase (5'-NTD) and acetylcholinesterase activities. CONCLUSION: The results suggest caffeic acid as a potent natural product with therapeutic effects against T2D. Further molecular and clinical studies are, however, required to ascertain these findings.

Harpephyllum caffrum fruit (wild plum) facilitates glucose uptake and modulates metabolic activities linked to neurodegeneration in isolated rat brain: An in vitro and in silico approach.

Alteration in brain glucose metabolism due to glucose uptake reduction has been described in the onset of certain neurodegenerative disorders. This study determined Harpephyllum caffrum fruit's potential ability to improve glucose uptake and its modulatory effects on intrinsic antioxidant, glucogenic, cholinergic, and nucleotide-hydrolyzing enzyme activities in isolated rat brain. Consequently, the bioactive compounds of the fruits were identified with LC-MS. The fruit significantly improved brain glucose uptake following coincubation with glucose and brain tissue. The fruit extract also elevated GSH level, SOD, catalase, glycogen phosphorylase, and ENTPDase activities while simultaneously suppressing NO and malonaldehyde levels and fructose-1,6-bisphosphatase, ATPase, acetylcholinesterase and butyrylcholinesterase activities. LC-MS analysis revealed S-methylcysteine sulfoxide, dihydroquercetin, 3,4-dimethyl-2,5-bis(3,4,5-trimethoxyphenyl) tetrahydrofuran (MTHF), nobiletin, puerarin, quercetin 3-rutinoside, 8-D-glucosyl-4',5,7-trihydroxyflavone, asperulosidic acid, 1,2,4,6-tetragalloylglucose, and phellamurin. This study suggests the neuroprotective effects of H. caffrum fruit due to its ability to enhance glucose uptake, attenuate glucose-induced oxidative stress while modulating glucogenic, cholinergic, and nucleotide-hydrolyzing enzyme activities in normal brain tissues. PRACTICAL APPLICATIONS: Available scientific evidence describes oxidative stress as one of the physiological processes contributing to aging-associated neurodegeneration in humans. In this regard, commonly consumed natural products from plants have attracted much interest due to their ability to mitigate redox imbalance-related pathologies that affect various organs in the body such as the brain. Harpephyllum caffrum or bush mango is an evergreen plant native to the South African vegetation. The fruit from the plant is consumed locally as food or specifically for improving the nutritional quality of meals as deserts or condiments. While previous findings described the high antioxidant properties of the fruits, this study reported possible mechanisms via which the plant may exhibit ameliorative effects against oxidative stress-related neurological disorders in the brain. Hence, findings from the current work present another justification for the significance of fruits as a safer nutraceutical alternative for therapy in neurological disease management.

Cannabidiol improves glucose utilization and modulates glucose-induced dysmetabolic activities in isolated rats' peripheral adipose tissues.

Reduced glucose uptake and utilization, with concomitant lipolysis in adipose tissues has been linked to the pathogenesis of obesity and its complications. The present study investigated the effect of cannabinoid-stimulated glucose uptake on redox imbalance, glucose and lipid metabolisms, as well as cholinergic and purinergic dysfunctions in isolated rats' adipose tissues. Freshly Isolated rats' adipose tissues were incubated with glucose and different concentrations of cannabidiol for 2 h at 37 °C. The negative control consisted of incubation without cannabidiol, while normal control consisted of incubations without glucose and/or cannabidiol and Metformin served as the standard drug. Cannabidiol caused an increase in adipose-glucose uptake, with concomitant elevation of glutathione, triglyceride level, superoxide dismutase, catalase and 5'nucleoidase activities. It also caused suppression in malondialdehyde and cholesterol levels, acetylcholinesterase, ENTPDase, fructose-1,6-biphosphatase, glucose 6-phosphatase, glycogen phosphorylase, and lipase activities. In silico studies revealed a strong molecular interaction of cannabidiol with adipose triglyceride lipase, hormone-sensitive lipase, and monoglyceride lipase. These results indicate that cannabidiol-enhanced glucose uptake in adipose tissues is associated with enhanced antioxidative activities, concomitant modulation of cholinergic and purinergic dysfunctions, and improved glucose - lipid homeostasis.

A study of structure-activity relationship and anion-controlled quinolinyl Ag(I) complexes as antimicrobial and antioxidant agents as well as their interaction with macromolecules.

In this communication, we feature the synthesis and in-depth characterization of a series of silver(I) complexes obtained from the complexation of quinolin-4-yl Schiff base ligands ((E)-2-((quinolin-4-ylmethylene)amino)phenol La, 2-(quinolin-4-yl)benzo[d]thiazole Lb, (E)-N-(2-fluorophenyl)-1-(quinolin-4-yl)methanimine Lc, (E)-N-(4-chlorophenyl)-1-(quinolin-4-yl)methanimine Ld, (E)-1-(quinolin-4-yl)-N-(p-tolyl)methanimine Le, (E)-1-(quinolin-4-yl)-N-(thiophen-2-ylmethyl)methanimine Lf) and three different silver(I) anions (nitrate, perchlorate and triflate). Structurally, the complexes adopted different coordination geometries, which included distorted linear or distorted tetrahedral geometry. The complexes were evaluated in vitro for their potential antibacterial and antioxidant activities. In addition, their interactions with calf thymus-DNA (CT-DNA) and bovine serum albumin (BSA) were evaluated. All the complexes had a wide spectrum of effective antibacterial activity against gram-positive and gram-negative bacterial and good antioxidant properties. The interactions of the complexes with CT-DNA and BSA were observed to occur either through intercalation or through a minor groove binder, while the interaction of the complexes with BSA reveals that some of the complexes can strongly quench the fluorescence of BSA through the static mechanism. The molecular docking studies of the complexes were also done to further elucidate the modes of interaction with CT-DNA and BSA.

Ferulic acid promotes muscle glucose uptake and modulate dysregulated redox balance and metabolic pathways in ferric-induced pancreatic oxidative injury.

The antidiabetic properties of ferulic acid and its protective role against Fe2+ -induced oxidative pancreatic injury were investigated in this study using in vitro and ex vivo models. Induction of oxidative injury in the pancreas was achieved by incubating normal pancreatic tissue with 0.1 mM FeSO4 and treated by co-incubating with different concentrations of ferulic acid for 30 min at 37°C. Ferulic acid inhibited the activities of α-glucosidase, α-amylase, and pancreatic lipase significantly (p < .05) and promoted glucose uptake in isolated rat psoas muscles. Induction of oxidative pancreatic injury caused significant (p < .05) depletion of glutathione (GSH) level, superoxide dismutase (SOD), and catalase activities, as well as elevation of malondialdehyde (MDA) and nitric oxide (NO) levels, acetylcholinesterase and chymotrypsin activities. Treatment of tissues with ferulic acid significantly (p < .05) reversed these levels and activities. LC-MS analysis of the extracted metabolites revealed 25% depletion of the normal metabolites with concomitant generation of m-Chlorohippuric acid, triglyceride, fructose 1,6-bisphosphate, and ganglioside GM1 in oxidative-injured pancreatic tissues. Treatment with ferulic acid restored uridine diphosphate glucuronic acid and adenosine tetraphosphate and generated P1,P4-Bis(5'-uridyl) tetraphosphate and L-Homocysteic acid, while totally inactivating oxidative-generated metabolites. Ferulic acid also inactivated oxidative-activated pathways, with concomitant reactivation of nucleotide sugars metabolism, starch and sucrose metabolism, and rostenedione metabolism, estrone metabolism, androgen and estrogen metabolism, porphyrin metabolism, and purine metabolism pathways. Taken together, our results indicate the antidiabetic and protective potential of ferulic acid as depicted by its ability to facilitate muscle glucose uptake, inhibit carbohydrate and lipid hydrolyzing enzymes, and modulate oxidative-mediated dysregulated metabolisms. PRACTICAL APPLICATIONS: There have been increasing concerns on the side effects associated with the use of synthetic antidiabetic drug, coupled with their expenses particularly in developing countries. This has necessitated continuous search for alternative treatments especially from natural products having less or no side effects and are readily available. Ferulic acid is among the common phenolics commonly found in fruits and vegetables. In this present study, ferulic acid was able to attenuate oxidative stress, cholinergic dysfunction, and proteolysis in oxidative pancreatic injury, as well as inhibit carbohydrate digesting enzymes. Thus, indicating the ability of the phenolic to protect against complications linked to diabetes. Crops rich in ferulic acid maybe beneficial in managing this disease.

Microstructural and chemical properties of gari and eba: Food products from cassava (Manihot esculenta Cranz).

The microstructure, elemental distribution and rheological behavior of two varieties of gari and their doughs (eba) were investigated. SEM analysis revealed a concave structure with fibre-strands, which were altered after processing to eba. Gari nanostructures which were analyzed with TEM were not affected when processed to eba. SEM-EDX microanalysis revealed the presence of magnesium, potassium, calcium, manganese, iron, and cobalt for both varieties, which were altered after processing. Rheological analysis revealed increases in storage modulus, with concomitant loss factor for both varieties. Their viscosity decreased with increasing shear rate. GC-MS analysis revealed the presence of sugar, fatty acids, and steroids in both varieties, which were also affected after processing. Both varieties showed significant free radical scavenging activity which was not affected after processing. These results indicate that the conclave microstructure, elements and phytochemicals of both gari varieties are altered after processing to eba, with their nanostructure and antioxidant activity unaltered.

The antioxidant and antidiabetic potentials of polyphenolic-rich extracts of Cyperus rotundus (Linn.).

In this study, the rhizome of Cyperus rotundus L was investigated for its antioxidant and antidiabetic effects using in vitro and in silico experimental models. Its crude extracts (ethyl acetate, ethanol and aqueous) were screened in vitro for their antioxidant activity using ferric-reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH), as well as their inhibitory effect on α-glucosidase enzyme. Subsequently, the extracts were subjected to Gas Chromatography-Mass Spectrometry (GC-MS) analysis to elucidate their possible bioactive compounds. Furthermore, computational molecular docking of selected phenolic compounds was conducted to determine their mode of α-glucosidase inhibitory activity. The aqueous extract displayed the highest level of total phenolic content and significantly higher scavenging activity in both FRAP and DPPH assays compared to ethyl acetate and ethanol extracts. In FRAP and DPPH assays, IC50 values of aqueous extract were 448.626 µg/mL and 418.74 µg/mL, respectively. Aqueous extract further presented higher α-glucosidase inhibitory activity with an IC50 value of 383.75 µg/mL. GC-MS analysis revealed the presence of the following phenolic compounds: 4-methyl-2-(2,4,4-trimethylpentan-2-yl) phenol, Phenol,2-methyl-4-(1,1,3,3-tetramethylbutyl)- and 1-ethoxy-2-isopropylbenzene. Molecular docking study revealed 1-ethoxy-2-isopropylbenzene formed two hydrogen bonds with the interacting residues in the active site of α-glucosidase enzyme. Furthermore, 4-methyl-2-(2,4,4-trimethylpentan-2-yl) phenol had the lowest binding energy inferring the best affinity for α-glucosidase active site. These results suggest the possible antioxidant and antidiabetic potential of Cyperus rotundus.Communicated by Ramaswamy H. Sarma.

Vanillin improves glucose homeostasis and modulates metabolic activities linked to type 2 diabetes in fructose-streptozotocin induced diabetic rats.

OBJECTIVE: This study investigated the antidiabetic effect of vanillin using in vitro, in silico, and in vivo experimental models. METHODOLOGY: Type 2 diabetes (T2D) was induced in male Sprague-Dawley (SD) rats using fructose-streptozotocin (STZ) , then orally administered low (150 mg/kg bodyweight) or high (300 mg/kg bodyweight) dose of vanillin for 5 weeks intervention period. RESULTS: Vanillin suppressed the levels of blood glucose, serum cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-c), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea, uric acid, when elevated serum insulin, HDL-cholesterol, and concomitantly improved pancreatic ß-cell function, glucose tolerance, and pancreatic morphology. It also elevated both serum and pancreatic tissue GSH level, SOD and catalase activities, and hepatic glycogen level, while depleting malondialdehyde level, α-amylase, lipase, acetylcholinesterase, ATPase, ENTPDase and 5'-nucleotidase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glycogen phosphorylase activities. CONCLUSIONS: The results indicate the potent antidiabetic effect of vanillin against T2D and its associated complications.

Vanillin modulates activities linked to dysmetabolism in psoas muscle of diabetic rats.

Skeletal muscles are important in glucose metabolism and are affected in type 2 diabetes (T2D) and its complications. This study investigated the effect of vanillin on redox imbalance, cholinergic and purinergic dysfunction, and glucose-lipid dysmetabolism in muscles of rats with T2D. Male albino rats (Sprague-Dawley strain) were fed 10% fructose ad libitum for 2 weeks before intraperitoneally injecting them with 40 mg/kg streptozotocin to induce T2D. Low (150 mg/kg bodyweight (BW)) and high (300 mg/kg BW) doses of vanillin were orally administered to diabetic rats. Untreated diabetic rats and normal rats made up the diabetic control (DC) and normal control (NC) groups, respectively. The standard antidiabetic drug was metformin. The rats were humanely put to sleep after 5 weeks of treatment and their psoas muscles were harvested. There was suppression in the levels of glutathione, activities of SOD, catalase, ENTPDase, 5'Nucleotidase and glycogen levels on T2D induction. This was accompanied by concomitantly elevated levels of malondialdehyde, serum creatine kinase-MB, nitric oxide, acetylcholinesterase, ATPase, amylase, lipase, glucose-6-phosphatase (G6Pase), fructose-1,6-biphophastase (FBPase) and glycogen phosphorylase activities. T2D induction further resulted in the inactivation of fatty acid biosynthesis, glycerolipid metabolism, fatty acid elongation in mitochondria and fatty acid metabolism pathways. There were close to normal and significant reversals in these activities and levels, with concomitant reactivation of the deactivated pathways following treatment with vanillin, which compared favorably with the standard drug (metformin). Vanillin also significantly increased muscle glucose uptake ex vivo. The results suggest the therapeutic effect of vanillin against muscle dysmetabolism in T2D as portrayed by its ability to mitigate redox imbalance, inflammation, cholinergic and purinergic dysfunctions, while modulating glucose-lipid metabolic switch and maintaining muscle histology.