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The glycemic control potential and flavonoid profile of litchi have been documented for its hydroalcoholic extracts, while there is scarce information regarding its ethyl acetate extract. This study investigated the flavonoid profile, as well as the ameliorative potential and possible underlying mechanisms of litchi peel ethyl acetate extract on type 2 diabetes-related pathologies in a fructose/streptozotocin (STZ) model of diabetic rats. Sprague Dawley rats were induced with diabetes by administering 10% fructose for 2 weeks and a single i.p. injection of low-dose (40 mg/kg bw) STZ. Thereafter, the animals were orally administered with a low-dose (150 mg/kg bw) and high-dose (300 mg/kg bw) of the peel extract (LDPE and HDPE, respectively) and metformin (200 mg/kg bw). Compared to untreated diabetic rats (AUC = 1004 mg.h/dL), the HDPE significantly (p < 0.05) improved glucose tolerance (AUC = 847 mg.h/dL), which was statistically comparable (p ˃ 0.05) to the effect of metformin (AUC = 903 mg.h/dL). Serum insulin and pancreatic histology data showed that the STZ-induced pancreatic damage and insulin depletion was improved by the HDPE, which could be linked to the observed ameliorative effect of the extract on pancreatic lipid peroxidation and SOD and catalase activity. The extract further improved liver and muscle glycogen storage, as well as muscle hexokinase activity and Akt phosphorylation, suggesting that the extract exerts glycemic control by enhancing glycogen storage and modulating insulin-mediated signaling of glucose uptake and utilization. LC-MS data and documented reports suggest that flavonoids, such as epicatechin, cinnamtannin B2, procyanidin B5, and proanthocyanidin A2, are the possible influencing compounds. The ethyl acetate extract of litchi peel could be a source of bioactive flavonoids that can potentiate glycemic control in diabetes and mitigate oxidative stress-related pathologies. [ABSTRACT FROM AUTHOR]

Bioactive flavonoid epicatechin has been reported in the peel of litchi fruit but isolated from its hydroalcoholic extracts. This study isolated epicatechin with cellular glucose uptake modulatory and ROS production inhibitory properties from the ethyl acetate (EtOAc) extract using a bioassay-guided approach. The fruit peel was defatted with hexane and sequentially extracted using dichloromethane (DCM), EtOAc, methanol (MeOH) and water. In vitro phytochemical models, namely antioxidant (Fe3+ reducing, radical scavenging and anti-linoleic acid peroxidative) and glycaemic control (α-glucosidase and α-amylase inhibitory and glucose uptake modulatory), were employed for the bioassay-guided isolation, while the isolated compound was characterised using NMR and mass spectrometry and assessed for dose-dependent inhibition of α-glucosidase and lipopolysaccharide (LPS)-induced cellular ROS production, as well as modulation of cellular glucose uptake. Relative to the other extracts, the EtOAc extract had appreciable phenol and flavonoid contents, which perhaps influenced its potent anti-lipid peroxidative (65.0%) and α-glucosidase inhibitory (52.4%) effects. The α-glucosidase inhibitory potency of the fractions (1–8) from the EtOAc extracts correlated with their flavonoid contents, with fraction 5 outperforming other fractions. The fraction comprised a pool of fractions obtained from the DCM:MeOH:water (7:3:0.281 v/v/v) solvent system. LC-MS revealed the predominant presence of epicatechin in fraction 5, which was later isolated from one of the sub-fractions (sub-fraction 4) of fraction 5. This sub-fraction had stronger anti-lipid peroxidative (65.5%), α-glucosidase inhibitory (65.8%) and glucose uptake modulatory (38.2%) effects than the other sub-fractions from fraction 5, which could have been influenced by the isolated epicatechin. Moreover, the isolated epicatechin inhibited α-glucosidase (IC50 = 35.3 µM), modulated cellular glucose uptake (EC50 = 78.5 µM) and inhibited LPS-induced ROS production in RAW 264.7 macrophages in a dose-dependent fashion [IC50 = 18.9 µM; statistically comparable (p > 0.05) to ascorbic acid, IC50 = 9.57 µM]. Epicatechin from litchi peel EtOAc extract could potentiate glucose uptake modulatory, α-glucosidase inhibitory and ROS suppressive capacities, which could be influential in the use of litchi fruit peel for managing diabetes and associated oxidative damage. [ABSTRACT FROM AUTHOR]

Year after year, there are more cases of cancer, sparking questions about the effectiveness of available treatments. As a result, patients are searching for new therapies to supplement and/or replace radiotherapy, surgery, and chemotherapy. Graviola and other plants have been found to contain phytochemicals compounds that could be employed to cure cancer. This review seeks to highlight the phytochemicals from A. muricata as possible anticancer agents, taking into account the increasing inadequacies of cancer treatments provided by healthcare facilities. Graviola's potential to suppress malignant cell proliferation while having minimal to no impact on normal cell survival has been demonstrated in vitro and in vivo systems against a wide range of human cancers and pathogens. The antioxidant property of bioactive principles in A. muricata appears to influence the anticancer potentials of the plant. Graviola extracts made from various plant parts have been found to have a variety of phytochemical components. Phenols, alkaloids, acetogenins and essential oils are the most important phytochemical components isolated. In vivo and in vitro studies have revealed that A. muricata extracts and bioactive compounds have anticancer and antioxidant properties. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

According to a survey, the medicinal use of Androstachys johnsonii Prain is kept secret by traditional healers. Considering that inflammation and oxidative stress are major risk factors for the progression of various chronic diseases and disorders, we resolved to investigate the antioxidant and anti-inflammatory potentials of A. johnsonii using in vitro and cell-based assays. The antioxidant activity of A. johnsonii hydroethanolic leaf extract (AJHLE) was evaluated using the ABTS, DPPH, and FRAP assays. Its cytotoxic effect was assessed on RAW 264.7 macrophages using an MTT assay. Then, its anti-inflammatory effect was evaluated by measuring the NO production and 15-LOX inhibitory activities. Moreover, its preventive effect on ROS production and its regulatory effect on the expression of pro-inflammatory mediators such as IL-1β, IL-10, TNF-α, and COX-2 were determined using established methods. AJHLE strongly inhibited radicals such as ABTS•+, DPPH•, and Fe3+-TPTZ with IC50 values of 9.07 µg/mL, 8.53 µg/mL, and 79.09 µg/mL, respectively. Additionally, AJHLE induced a significant (p < 0.05) cytotoxic effect at 100 µg/mL, and when tested at non-cytotoxic concentrations, it inhibited NO and ROS production in LPS-stimulated RAW 264.7 macrophages in a concentration-dependent manner. Furthermore, AJHLE showed that its anti-inflammatory action occurs via the inhibition of 15-LOX activity, the downregulation of COX-2, TNF-α, and IL-1β expression, and the upregulation of IL-10 expression. Finally, chemical investigation showed that AJHLE contains significant amounts of procyanidin, epicatechin, rutin, and syringic acid which support its antioxidant and anti-inflammatory activities. These findings suggest that A. johnsonii is a potential source of therapeutic agents against oxidative stress and inflammatory-related diseases. [ABSTRACT FROM AUTHOR]

The present study investigated the effect of coconut water on glucose uptake and utilization, and metabolic activities linked to hyperglycemia in isolated rat psoas muscles. Coconut water was subjected to in vitro antioxidant and antidiabetic assays, which cover 2,2′-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, ferric reducing antioxidant power (FRAP), and inhibition of α-glucosidase and α-amylase activities. Psoas muscles were isolated from male Sprague Dawley rats and incubated with coconut water in the presence of glucose. Control consisted of muscles incubated with glucose only, while normal control consisted of muscles not incubated in coconut water and/or glucose. The standard antidiabetic drug was metformin. Incubation with coconut water led to a significant increase in muscle glucose uptake, with concomitant exacerbation of glutathione level, and SOD and catalase activities, while suppressing malondialdehyde level, and ATPase and E-NTDase activities. Coconut water showed significant scavenging activity against DPPH, and significantly inhibited α-glucosidase and α-amylase activities. LC-MS analysis of coconut water revealed the presence of ellagic acid, butin, quercetin, protocatechuic acid, baicalin, and silibinin. Molecular docking analysis revealed potent molecular interactions between the LC-MS-identified compounds, and AKT-2 serine and PI-3 kinase. These results indicate the potential of coconut water to enhance glucose uptake, while concomitantly improving antioxidative and purinergic activities. They also indicate the potential of coconut water to suppress postprandial hyperglycemia. These activities may be attributed to the synergistic effects of the LC-MS-identified compounds. [ABSTRACT FROM AUTHOR]

Diabetes mellitus and related metabolic and vascular impairments are notable health problems. Fruits and vegetables contain phenolics that are beneficial to metabolic and oxidative health and useful in preventing associated disease. Scientific evidence has shown that some bioactive phenolics are more abundant in the non-edible parts (especially the peels) of many fruits than in their respective edible tissues. Fruits belonging to the Citrus and Prunus genera are commonly consumed worldwide, including in South Africa, and their non-edible wastes (peel and seed) have been shown to have antioxidative, metabolic and vascular pharmacological potentials and medicinal phytochemistry. It is therefore imperative to evaluate the pharmacological actions and phytochemical properties of the non-edible wastes of these fruits and understand how they could potentially be of medicinal relevance in oxidative, metabolic and vascular diseases, including diabetes, oxidative stress, obesity, hypertension and related cardiovascular impairments. In the absence of a previous review that has concomitantly presented the medicinal potentials of fruits wastes from both genera, this review presents a critical analysis of previous and recent perspectives on the medicinal potential of the non-edible wastes from the selected Citrus and Prunus fruits in metabolic, vascular and oxidative health. This review further exposes the medicinal phytochemistry, while elucidating the underlying mechanisms through the fruit wastes potentiates their therapeutic effects. A literature search was carried out on "PubMed" to identify peer-reviewed published (mostly 2015 and beyond) studies reporting the antidiabetic, antioxidative, antihypertensive, anti-hyperlipidemic and anti-inflammatory properties of the non-edible parts of the selected fruits. The data of the selected studies were analyzed to understand the bioactive mechanisms, bioactive principles and toxicological profiles. The wastes (seed and peel) of the selected fruits had antioxidant, anti-obesogenic, antihypertensive, anti-inflammatory, antidiabetic and tissue protective potentials. Some phenolic acids and terpenes, as well as flavonoids and glycosides such as narirutin, nobiletin, hesperidin, naringin, naringenin, quercetin, rutin, diosmin, etc., were the possible bioactive principles. The peel and seed of the selected fruits belonging to the Citrus and Prunus genera are potential sources of bioactive compounds that could be of medicinal relevance for improving oxidative, metabolic and vascular health. However, there is a need for appropriate toxicological studies. [ABSTRACT FROM AUTHOR]

Summary: Pomegranate peel contains bioactive ellagitannins including punicalagin, a major bioactive principle. However, studies have not optimally recovered and evaluated these ellagitannins for their antioxidant and glycaemic control potential. In the present study, a temperature‐dependent extraction was employed to optimally recover bioactive ellagitannins and punicalagin from pomegranate (variety 'Wonderful') peel. The peel was extracted with distilled water at different temperatures (25, 37, 50, 65, 78 and 95 °C) and evaluated for phenol and flavonoid contents, in vitro antioxidant and enzyme inhibitory activities. XAD16N resin was used to recover tannins from the extracts and punicalagin was purified from the tannin recovered from the 78 °C crude extract. LC–MS was used to characterise the ellagitannins profile. The dose‐dependent anti‐lipid peroxidative and glucose uptake potential of the punicalagin and its parent crude extract and tannin were measured. The extract obtained at 78 °C had the highest phenolic, flavonoid, tannin and punicalagin contents, which potentiated stronger radical scavenging, ORAC (IC50 = 9.64 vs. 15.6 and 25.6 μg/mL, respectively), anti‐linoleic acid peroxidative (IC50 = 9.97 vs. 19.9 and 27.3 μg/mL, respectively) and antiglycation (IC50 = 29.1 vs. 34.2 and 79.1 μg/mL, respectively) activities than the extract and the purified punicalagin. Similarly, the cellular anti‐lipid peroxidative and glucose modulatory effects of the recovered tannin (IC50 = 3.67 μg/mL; EC50 = 14.8 μg/mL) better than that of the extract (IC50 = 24.3 μg/mL; EC50 = 55.0 μg/mL) and the purified punicalagin (IC50 = 59.0 μg/mL; EC50 = 112 μg/mL), which may be attributed to the complementary action of the tannin's constituent compounds (punicalagin, ellagic acid, granatin A, corilagin, casuarinin, gallic acid and quercetin hexoside). The α‐amylase inhibitory data, however, suggest the purified punicalagin influences enzyme inhibitory potential of pomegranate peel. The study suggests tannin/ellagitannin purified from pomegranate peel aqueous extract obtained at 78 °C may be a promising dietary supplement for exerting glycaemic control and mitigating oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Sarcocephalus pobeguinii (Hua ex Pobég) is used in folk medicine to treat oxidative-stress related diseases, thereby warranting the investigation of its anticancer and anti-inflammatory properties. In our previous study, the leaf extract of S. pobeguinii induced significant cytotoxic effect against several cancerous cells with high selectivity indexes towards non-cancerous cells. Aim: The current study aims to isolate natural compounds from S. pobeguinii, and to evaluate their cytotoxicity, selectivity and anti-inflammatory effects as well as searching for potential target proteins of bioactive compounds. Methods: Natural compounds were isolated from leaf, fruit and bark extracts of S. pobeguinii and their chemical structures were elucidated using appropriate spectroscopic methods. The antiproliferative effect of isolated compounds was determined on four human cancerous cells (MCF-7, HepG2, Caco-2 and A549 cells) and non-cancerous Vero cells. Additionally, the anti-inflammatory activity of these compounds was determined by evaluating the nitric oxide (NO) production inhibitory potential and the 15-lipoxygenase (15-LOX) inhibitory activity. Furthermore, molecular docking studies were carried out on six putative target proteins found in common signaling pathways of inflammation and cancer. Results: Hederagenin (2), quinovic acid 3-O-[α-D-quinovopyranoside] (6) and quinovic acid 3-O-[β-D-quinovopyranoside] (9) exhibited significant cytotoxic effect against all cancerous cells, and they induced apoptosis in MCF-7 cells by increasing caspase-3/-7 activity. (6) showed the highest efficacy against all cancerous cells with poor selectivity (except for A549 cells) towards noncancerous Vero cells; while (2) showed the highest selectivity warranting its potential safety as a chemotherapeutic agent. Moreover, (6) and (9) significantly inhibited NO production in LPS-stimulated RAW 264.7 cells which could mainly be attributed to their high cytotoxic effect. Besides, the mixture nauclealatifoline G and naucleofficine D (1), hederagenin (2) and chletric acid (3) were active against 15-LOX as compared to quercetin. Docking results showed that JAK2 and COX-2, with the highest binding scores, are the potential molecular targets involved in the antiproliferative and anti-inflammatory effects of bioactive compounds. Conclusion: Overall, hederagenin (2), which selectively killed cancer cells with additional anti-inflammatory effect, is the most prominent lead compound which may be further investigated as a drug candidate to tackle cancer progression. [ABSTRACT FROM AUTHOR]

Despite the medicinal uses of Phragmanthera capitata, Globimetula dinklagei and Tapinanthus bangwensis against memory loss, convulsions and pain, their efficacy against brain-dysfunction diseases and inflammation models has not yet been studied. Therefore, this study aims to investigate the anti-inflammatory and acetylcholinesterase (AChE) inhibitory potentials of their crude extracts and isolated natural compounds by combining in vitro and in silico experiments. Crude extracts and isolated compounds were tested in vitro for their AChE inhibitory activity by using Ellman's method. Additionally, their anti-inflammatory activity was determined by evaluating the nitric oxide (NO) production inhibitory activity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells and the 15-lipoxygenase (15-LOX) inhibitory activity by using the ferrous oxidation xylenol orange assay. Furthermore, the in silico efficacy of natural compounds was investigated against ten putative target enzymes relevant in Alzheimer's disease (AD) pathogenesis and inflammation. It was found that the crude extracts had weak to moderate inhibitory potential against AChE, with the extract of T. bangwensis being the most active (50% inhibitory concentration (IC50) = 48.97 µg/mL). Six natural compounds, namely, 3-O-β-D-glucopyranosyl-28-hydroxy-α-amyrin (2), apigenin- 8-C-β-D-glucopyranoside (3), globimetulin B (5), globimetulin C (6), bangwaursene B (8) and 3β-acetoxy-11,12-epoxytaraxerol (9), were identified for the first time as having anti-AChE potential, among which (9) had the highest efficacy with an IC50 of 13.89 µM. Among the anti-AChE compounds, (5) was also efficient against NO production and 15-LOX, and the data are in agreement with the docking score. In summary, compounds (5) and (9) are the most prominent lead compounds that should be further tested experimentally against molecular targets of AD and inflammation. [ABSTRACT FROM AUTHOR]

Natural supplements are important in diabetes and oxidative stress management. A complexation‐mediated antihyperglycemic and antioxidant synergism between zinc(II) and p‐coumaric acid was investigated. p‐Coumaric acid was complexed with ZnSO4 and characterized by FT‐IR, 1H NMR, and mass spectroscopy. The antioxidant and antihyperglycemic potential of the complex and precursors were evaluated with different experimental models. Molecular docking with target proteins linked to diabetes was performed. A Zn(II)‐bicoumarate.2H2O complex was formed. The in vitro radical scavenging, α‐glucosidase inhibitory, antiglycation, and anti‐lipid peroxidative activities of the complex were several folds stronger than p‐coumaric acid. In Chang liver cells and rat liver tissues, the complex inhibited lipid peroxidation (IC50 = 56.2 and 398 μM) and GSH depletion (IC50 = 33.9 and 38.7 μM), which was significantly stronger (2.3–5.4‐folds) than p‐coumaric acid and comparable to ascorbic acid. Zn(II) and p‐coumaric synergistically modulated (1.7‐ and 2.8‐folds than p‐coumaric acid) glucose uptake in L‐6 myotubes (EC50 = 10.7 μM) and rat muscle tissue (EC50 = 428 μM), which may be linked to the observed complexation‐mediated increase in tissue zinc uptake. Glucose uptake activity was accompanied by increased hexokinase activity, suggesting increased glucose utilization. Docking scores α‐glucosidase, GLUT‐4, and PKB/Akt showed stronger interaction with the complex (−6.31 to −6.41 kcal/mol) compared to p‐coumaric acid (−7.18 to −7.74 kcal/mol), which was influenced by the Zn(II) and bicoumarate moieties of the complex. In vitro, the complex was not hepatotoxic or myotoxic. Zn(II) complexation may be a therapeutic approach for improving the antioxidative and glycemic control potentials of p‐coumaric acid. Practical applications: In functional medicine, natural supplements, plant‐derived phenolics, and nutraceuticals are becoming popular in the management of diseases, including diabetes and oxidative stress. This has been largely attributed to their perceived holistic medicinal profile and the absence of notable toxicity concerns. In the past two decades, considerable attention has been drawn toward zinc mineral as a possible therapeutic supplement for diabetes due to its role in insulin secretion and reported insulin mimetic potentials. p‐Coumaric acid is a known natural antioxidant with reported diabetes‐related pharmacological effects. In this study, we took advantage of these properties and complexed both natural supplements, which resulted in a more potent nutraceutical with improved glycemic control and antioxidant potential. The complexation‐mediated synergistic interaction between zinc and p‐coumaric acid could be an important therapeutic approach in improving the use of these natural supplements or nutraceuticals in managing diabetes and associated oxidative complications. [ABSTRACT FROM AUTHOR]

Aim: This study was done to investigate the anti‐diabetic and anti‐oxidative synergism between zinc(II) and ferulic acid through complexation. Methods: Zinc sulphate was complexed with ferulic acid in a 1:2 molar ratio. The complex was characterized using Fourier‐transform infrared spectroscopy, proton NMR and high‐resolution mass spectroscopy techniques and evaluated for cellular toxicity. In silico, in vitro, cell‐based and tissue experimental models were used to test the anti‐diabetic and anti‐oxidant activities of the complex relative to its precursors. Results: A zinc(II)‐biferulate.2H2O complex was formed. The in vitro radical scavenging, anti‐lipid peroxidative and α‐glucosidase and α‐amylase inhibitory activity of the complex was 1.7–2.1 folds more potent than ferulic acid. Zn(II) complexation increased the anti‐glycation activity of ferulic acid by 1.5 folds. The complex suppressed lipid peroxidation (IC50 = 48.6 and 331 μM) and GHS depletion (IC50 = 33.9 and 33.5 μM) in both Chang liver cells and isolated rat liver tissue. Its activity was 2.3–3.3 folds more potent than ferulic acid and statistically comparable to ascorbic acid. Zn(II) complexation afforded ferulic acid improved glucose uptake activity in L‐6 myotube (EC50 = 11.7 vs. 45.7 μM) and isolated rat muscle tissue (EC50 = 501 and 1510 μM). Complexation increased muscle tissue zinc(II) uptake and hexokinase activity. Docking scores of the complex (−7.24 to −8.25 kcal/mol) and ferulic acid (−5.75 to 6.43 kcal/mol) suggest the complex had stronger interaction with protein targets related to diabetes, which may be attributed to the 2 ferulic acid moieties and Zn(II) in the complex. Moreover, muscle tissue showed increased phospho‐Akt/pan‐Akt ratio upon treatment with complex. The complex was not hepatotoxic and myotoxic at in vitro cellular level. Conclusion: Zn(II) complexation may be promising therapeutic approach for improving the glycaemic control and anti‐oxidative potential of natural phenolic acids. [ABSTRACT FROM AUTHOR]

The peel of pomegranate fruit contains antioxidant phytochemicals that may potentiate health benefits but remain under‐explored. We evaluated the antioxidant, nutritional and phytochemical profiles of the peel of the "Wonderful" variety pomegranate and its influence on oxidative metabolic alterations in hepatic tissue. The peel contained appreciable amounts of some beneficial trace minerals and both essential and non‐essential amino acids. Mostly Omega 3 and 6 fatty acids were found. The peel extracts exhibited in vitro radical scavenging and Fe3+ reducing antioxidant activities and dose‐dependently prevented oxidative stress‐induced lipid peroxidation increase and GSH depletion in both Chang liver cells (IC50 = 18.0 ± 1.46 and 11.2 ± 0.99 µg/mL, respectively) and isolated rat liver (IC50 = 96.7 ± 3.34 and 19.4 ± 3.36 µg/mL, respectively). The antioxidant effects were comparable to that of ascorbic and correlated with their phenolic profile. HPLC analysis further identified antioxidant phenolic acids (gallic acid, syringic acid ferulic acid p‐coumaric acid or trans‐4‐hydroxycinnamic acid, etc.). The peel did not cause notable cytotoxicity in liver and kidney cells, which suggest minimal safety concerns. Metabolomics analysis revealed alterations in fatty acid, amino acids, and nucleic acid metabolisms following the induction of oxidative stress. These alterations were improved in the acetone extract‐treated tissues, with concomitant activation of vitamin and selonocompound metabolisms. Data suggest that the fruit peel of "Wonderful" pomegranate may be an underutilized source of functional nutrients and antioxidants phenolic acids for optimum body function and mitigation hepatic oxidative damage and metabolic alterations as well as associated diseases. Practical applications: Although underutilized, documented evidence have shown that the wastes, like peels from fruits contain more phytochemicals than the edible pulp, making them potential sources of bioactive principles. In this study we exposed the nutritional, phytochemical and oxidative stress‐related medicinal benefits of the peel of "Wonderful" pomegranate variety. The peel could ameliorate oxidative hepatic metabolic alterations. The peel of this fruit could be a source of beneficial micro and macro nutrients, as well as bioactive phenolics to improve oxidative health and mitigate oxidative hepatic damage and associated disease states. Medicinally utilizing the fruit's peel could reduce underutilized fruit wastes, increase the value of the fruit and benefit the bioeconomy. [ABSTRACT FROM AUTHOR]

Objectives Our aim was to synthesize, characterize and evaluate the antihyperglycaemic and anti-oxidative properties of a new Zn(II) complex of vanillic acid. Methods The complex was synthesized using ZnSO4.7H2O and vanillic acid as precursors. NMR and FTIR techniques were used to characterize the synthesized complex. The cytotoxicity of the complex was measured. The antihyperglycemic and anti-oxidative properties of the complex were evaluated using in vitro, cell-based and ex vivo models and compared with those of its precursors. Key findings Zn(II) coordinated with vanillic acid via a Zn(O6) coordination, with the complex having three moieties of vanillic acid. The radical scavenging, Fe3+ reducing and hepatic antilipid peroxidative activity of the complex were, respectively, 2.3-, 1.8- and 9.7-folds more potent than vanillic acid. Complexation increased the α-glucosidase and glycation inhibitory activity of vanillic acid by 3- and 2.6-folds, respectively. Zn(II) conferred potent L-6 myotube (EC50 = 20.4 μ m) and muscle tissue (EC50 = 612 μ m) glucose uptake effects on vanillic acid. Cytotoxicity evaluation showed that the complex did not reduce the viability of L-6 myotubes and Chang liver cells. Conclusions The data suggest that Zn(II)–vanillic acid complex had improved bioactivity relative to vanillic acid. Thus, Zn(II) may be further studied as an antihyperglycaemic and anti-oxidative adjuvant for bioactive phenolic acids. [ABSTRACT FROM AUTHOR]

This study investigated the protective properties of strawberry fruit on testicular oxidative injury. Oxidative injury was induced in vitro in testicular tissue homogenates by incubation with ferrous sulphate (FeSO4) in the presence and absence of strawberry fruit extract (SFE) for 30 min at 37˚C, with gallic acid serving as the standard antioxidant drug. Induction of oxidative injury significantly reduced glutathione, cholesterol and triglyceride levels; and inhibited SOD, catalase and ENTPDase activities when compared to normal control. It also led to exacerbated nitric oxide, malondialdehyde, LDL‐cholesterol levels, acetylcholinesterase, ATPase and lipase activities. These effects were, however, reversed following treatment with SFE when compared to the untreated control, except for cholesterol and triglyceride levels. Additionally, the induction of the oxidative injury led to alterations in testicular lipid metabolites that were accompanied by the activation of α‐linolenic acid and linoleic acid metabolic pathways. While SFE treatment had no significant impact on the altered metabolites, it repressed pathways for mitochondrial beta‐oxidation of long‐chain saturated fatty acids and plasmalogen synthesis. High‐performance liquid chromatography analysis of SFE revealed the presence of rutin, caffeic acid, p‐coumarin and cinnamic acid. These data imply the protective potentials of strawberry fruits against testicular oxidative injury. [ABSTRACT FROM AUTHOR]

Cardiotoxicity leading to cardiovascular dysfunction and ultimately cardiac failure remains a major global health issue irrespective of race, age and country. Several factors including lipotoxicity, oxidative imbalance, exacerbated angiotensin-converting enzyme (ACE) activity and altered bioenergetics have been implicated in the pathophysiology of cardiovascular diseases. Turbina oblongata (E. Mey. ex Choisy) A. Meeuse is among the medicinal plants commonly used traditionally in the treatment and management of various ailments including cardiovascular dysfunctions in South Africa. In the present study, T. oblongata was investigated for its cardioprotective mechanism on oxidative-mediated cardiotoxicity by determining its effect on redox imbalance, purinergic and cholinergic dysfunction, and ACE activity as well as lipid dysmetabolism and pathways in iron-induced oxidative cardiac injury. Oxidative injury was induced ex vivo in freshly isolated heart by incubating with 0.1 mM FeSO4. Treatment was done by co-incubating with T. oblongata extract or gallic acid which served as the standard antioxidant. Induction of oxidative cardiac injury led to significant depleted levels of glutathione, triglyceride, HDL-cholesterol, superoxide, catalase and ENTPDase activities, with concomitant elevated levels of malondialdehyde, cholesterol, LDL-cholesterol, ACE, acetylcholinesterase, ATPase and lipase activities. These levels and activities were significantly reversed following treatment with T. oblongata. Induction of oxidative injury also caused alterations in lipid metabolites, with concomitant activation of beta oxidation of very long chain fatty acids, plasmalogen synthesis and mitochondrial beta-oxidation of long chain saturated fatty acids pathways. Some of the altered metabolites were restored following treatment with T. oblongata , with concomitant inactivation of beta oxidation of very long chain fatty acid pathway. These results indicate the cardioprotective effect of T. oblongata against oxidative-mediated cardiotoxicity. This is evidenced by its ability to mitigate lipotoxicity and modulate dysregulated cardiometabolic activities as portrayed by its antioxidative activity and suppressive effects on ACE, acetylcholinesterase and lipase activities, while modulating cardiac lipid dysmetabolism. [ABSTRACT FROM AUTHOR]

In this study, zinc was complexed with p‐hydroxybenzoic acid to synthesize a complex with improved pharmacological profile. Proton NMR and FTIR analysis were used to characterize the complex. Several in vitro, cellular and ex vivo antihyperglycemic and antioxidative assays were used to evaluate the potency of the complex, relative to its precursors, while molecular docking was used to investigate interactions with insulin signaling targets (GLUT‐4 and PKB). Also, the cytotoxicity of the complex was evaluated in Chang liver cells and L‐6 myotubes using MTT assay. Complexation was through a Zn(O4) coordination. This afforded the complex two moieties of p‐hydroxybenzoic acid, which influenced its activities. While the complex retained the α‐glucosidase and α‐amylase inhibitory activity of its phenolic acid precursor, complexation increased in vitro and ex vivo antioxidant activity of the phenolic acid by 1.4 to 10.5‐folds. Complexation, further, conferred a potent antiglycation activity and L‐6 myotube and psoas muscle glucose uptake properties (2.1 to 3.5‐folds more than p‐hydroxybenzoic acid) on the phenolic acid, without notably inhibiting or reducing the viability of Chang liver cells (IC50 = 5,120 μM) and L‐6 myotubes (IC50 = 2,172 μM). Docking studies showed the complex had better interactions with insulin signaling targets (GLUT‐4 and PKB) than p‐hydrobenzoic acid, which may influence its glucose uptake effects. Data suggest that Zn(II) complexation improved and/or broadened the pharmacological profile of p‐hydroxybenzoic acid, thus, may be further studied as a promising adjuvant for phenolic acids. Practical applications: Most antidiabetic drugs are used as two or more combinations to achieve better efficacy, which may cause drug interaction and increase the risk of side effects associated with these drugs. This study takes advantage of the glycemic control property of zinc and the antioxidant and/or diabetes‐related pharmacological properties of p‐hydroxybenzoic acid to form a complex with improved and broader antioxidant and antihyperglycemic profile and minimal toxicity concerns. With appropriate further studies, Zn(II)‐phenolic acid complexes may be safe nutraceuticals for diabetes and related oxidative complications. [ABSTRACT FROM AUTHOR]

Objectives: This study was done to synthesize a novel Zn(II)‐gallic acid complex with improved antidiabetic and antioxidative properties. Methods: The complex was synthesized and characterized using Fourier Transform Infrared (FT‐IR) and 1H NMR. Cytotoxicity was evaluated using Chang liver cells and L6 myotubes. Radical scavenging and Fe3+‐reducing, as well as α‐glucosidase, α‐amylase and glycation inhibitory properties were measured. Glucose uptake was measured in L6 myotubes, while the complex was docked against glucose transporter type 4 (GLUT‐4) and protein kinase B (PKB). Key findings: Analysis showed that complexation occurred through a Zn(O4) coordination; thus, the complex acquired two moieties of gallic acid, which suggests why complexation increased the DPPH (IC50 = 48.2 µm) and ABTS (IC50 = 12.7 µm) scavenging and α‐glucosidase inhibitory (IC50 = 58.5 µm) properties of gallic acid by several folds (5.5, 3.6 and 2.7 folds; IC50 = 8.79, 3.51 and 21.5 µm, respectively). Zn(II) conferred a potent dose‐dependent glucose uptake activity (EC50 = 9.17 µm) on gallic acid, without reducing the viability of L6 myotubes and hepatocytes. Docking analysis showed the complex had stronger interaction with insulin signalling proteins (GLUT‐4 and PKB) than its precursor. Conclusions: Data suggest that complexation of Zn(II) with gallic acid resulted in a complex with improved and multi‐facet antioxidative and glycaemic control properties. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is the most prominent of all diabetes types, contributing to global morbidity and mortality. Availability and cost of treatment with little or no side effect especially in developing countries, remains a huge burden. This has led to the search of affordable alternative therapies especially from medicinal plants. In this study, the antidiabetic effect of the methanolic extract, dichloromethane (DCM), butanol (BuOH) and aqueous fractions of Clerodendrum volubile leaves were investigated in type 2 diabetic rats for their effect on glucose homeostasis, serum insulin level and hepatic biomarkers, lipid profile, pancreatic redox balance and Ca2C levels, and b-cell distribution and function. The DCM was further fractionated to isolate the active compounds, biochanin and 5,7,40-trimethoxykaempferol. They were investigated for their toxicity and ADMET properties, a-glucosidase and angiotensin I converting enzyme (ACE) inhibitory activities in silico. There were significant (p < 0.05) decrease in blood glucose, cholesterol, LDL-C, vLDL-C, triglyceride, AST and ALT levels in all treated groups, with DCM fraction showing the best activity. All treated rats showed significantly (p < 0.05) improved anti-oxidative activities. Treatment with the DCM fraction led to significant (p < 0.05) increased serum insulin and pancreatic Ca2C levels, as well as improved b-cell distribution and function. DCM fraction also showed improved glucose tolerance. DCM fraction dose-dependently inhibited ACE activity. The toxicity class of the isolated compounds was predicted to be 5. They were also predicted to be potent inhibitors of cytochrome P (CYPs) 1A2, 2D6 and 3A4. They docked well with a-glucosidase and ACE. These results indicate the therapeutic potential of the plant against type 2 diabetes, with the DCM fraction being the most potent which may be attributed to the isolated flavones. It further suggests antihypertensive potentials of the DCM fraction. However, inhibition of CYPs by the flavones may suggest caution in usage with other prescribed drugs metabolized by these enzymes. [ABSTRACT FROM AUTHOR]

Senna occidentalis (L.) Link is a plant that has been used in medicine in some African countries, Asia and America. It is mainly used in Ayurvedic medicine in India. Several parts of this plant are used for preventing or treating diabetes, haematuria, rheumatism, typhoid, asthma, hepatotoxicity, disorders of haemoglobin and leprosy. This review outlines the pharmacological evidence supporting the potential of S. occidentalis to control or compensate for diabetes and associated complications, with intentions to sensitize the scientific community for future research on this promising plant. Information on the anti-diabetic pharmacological studies of Senna occidentalis was collected from various scientific databases including Scopus, PubMed, ScienceDirect and Google Scholar. The studies were analyzed for the toxicological, phytochemical, anti-diabetic, hypoglycemic, anti-hyperlipidemia and antioxidative aspects of the different parts of S. occidentalis. Numerous phytochemical constituents (flavonoids, saponins, alkaloids, tannins, terpenes and glycosides) are present in this plant and are responsible for their anti-diabetic, hypoglycemic, anti-hyperlipidemic and antioxidative effects. The different plant parts appears to exert anti-diabetic effects by direct regulation of blood glucose, modulation of lipid profile and improving of antioxidant status and islet function. Senna occidentalis is rich in phytochemicals. The crude extracts of the different parts have valuable bioactive properties with potential ethnopharmacological relevance for diabetes management and treatment. Further bioassay guided phytochemical analyses of this plant are recommended to explore its therapeutic bioactive principles. [Display omitted] • Diabetes is a metabolic disease that affects millions of people worldwide, characterized by hyperglycemia and dyslipidemia. • Detailed review on Senna occidentalis with anti-diabetic activities was conducted. • This plant showed anti-hyperglycemic, anti-hyperlipidemic and antioxidative effects. • Flavonoids, tannins, saponins, alkaloids, terpenes and glycosides were identified as potential phytochemicals. • Senna occidentalis could serve as a potential source to develop therapies against diabetes. [ABSTRACT FROM AUTHOR]

Buddleja saligna Willd (Loganiaceae), mostly indigenous to South Africa is traditionally used in the treatment cardio-dysfunctional related ailments amongst other diseases. The cardio-protective effect of B. saligna was investigated in ferric-induced oxidative cardiopathy. Hearts harvested from healthy male SD rats were incubated with 0.1 mM FeSO 4 to induce oxidative damage and co-incubated with B. saligna extract. Reaction mixtures without the extract served as negative control, while tissues without the extract or standard antioxidant (gallic acid) and pro-oxidant served as the normal control. The tissues were analyzed for levels of glutathione, malondialdehyde, and nitric oxide as well as cholinergic, angiotensin-converting enzyme (ACE), lipase, and purinergic enzymes activities, lipid profiles, fatty acid metabolic pathways and metabolites. Induction of oxidative damage significantly (p < 0.05) depleted the levels of GSH, SOD, catalase, and ENTPDase activities, while concomitantly elevating the levels of MDA, NO, ACE, acetylcholinesterase, lipase and ATPase activities. These levels and activities were significantly reversed on treatment with B. saligna. Treatment with B. saligna also led to depletion of cardiac cholesterol and LDL-c levels, while elevating triglyceride and HDL-c level. It also depleted oxidative-induced lipid metabolites with concomitant generation of thirteen other metabolites. B. saligna also inactivated oxidative-induced pathways for beta oxidation of very long chain fatty acids, glycerolipid metabolism, and fatty acid elongation in mitochondria. These results suggest that B. saligna protects against ferric-induced oxidative cardiopathy by mitigating oxidative stress, while concomitantly inhibiting ACE, acetylcholinesterase and lipase activities, and modulating lipid spectrum and dysregulated metabolic pathways. Image 1 [ABSTRACT FROM AUTHOR]

Quercetin was assessed for its antihyperglycemic effect in fructose‐streptozotocin (STZ) induced diabetic rats. The oral administration of quercetin at the dosage of 25 and 50 mg/kg for 28 days remarkably reduced the level of blood glucose, glycosylated hemoglobin (Hb), and hepatic glycogen but enhanced plasma Hb concentration. The altered activities of glucose‐6‐phosphatase and hexokinase in diabetic rats were significantly improved upon quercetin treatment. Furthermore, the antioxidant activity of pancreatic superoxide dismutase, catalase (CAT), and reduced glutathione was effectively increased while the value for thiobarbituric acid reactive species was decreased. A significant reduction of glycemia was observed in the glucose tolerance test, 120 min after the glucose pulse. Also, the damage caused by fructose‐STZ in the liver and pancreas of diabetic animals were restored to near normal. Molecular docking of quercetin showed a high affinity for hexokinase and CAT with a binding energy of −7.82 and −9.83 kcal/mol, respectively, more elevated than the standard drugs. Practical applications: Functional foods and nutraceuticals have increasingly interested the consumers in terms of health benefits and have started focussing on the prevention or cure of disease by the foods and their health‐enhancing phytochemicals. Quercetin is one of the most potent naturally occurring antioxidants within the flavonoid subclasses, mostly distributed as a secondary metabolite in fruits, vegetables, and black tea. Based on the results exhibited in the present study, we proposed that the consumption of foods rich in quercetin could be a cheap and affordable nutraceutical that can be developed for the treatment of T2DM and its complications. Further studies on the safety aspects of quercetin in long‐term usage are strongly recommended before implementing for the treatment of human diseases. [ABSTRACT FROM AUTHOR]

Raffia palm wine is a natural drink from the stem of Raffia palm (Raphia hookeri) tree with nutritional and medicinal properties. The effect of fermentation was investigated on its antidiabetic and antioxidative effects in yeast cells and pancreatic tissues, respectively. Both unfermented and fermented palm wine significantly increased glucose uptake, reduced glutathione level (GSH), superoxide dismutase, and catalase activities. They also inhibited glucose diffusion, myeloperoxidase, and ATPase activities as well as decreased malondialdehyde and nitric oxide levels. They also led to the inactivation of oxidative metabolic pathways in oxidative pancreas with the generation of adenosine, sugar and inositol metabolites, selenium (enzyme co‐factor) and vitamin metabolites owing to concomitant activation of vitamins, lipid, steroids, inositol, and sulfate/sulfite metabolic pathways. The results suggest the antidiabetic and antioxidative potentials of unfermented and fermented palm wine and may be attributed to the LC‐MS‐identified compounds which were mainly polyphenols and its glycosides, vitamins, and amino acids. Practical applications: Raffia palm wine is among the natural beverages employed for social, nutritional, and medicinal purposes. However, there are limited studies on its medicinal properties. This study reports for the first time, the ability of Raffia palm wine to stimulate glucose uptake, inhibit glucose diffusion, and ameliorate pancreatic oxidative injury, as well as the possible associated metabolic pathways that may be involved. These findings will further contribute in understanding the antidiabetic effect of Raffia palm wine, and the possible metabolic pathways involved. [ABSTRACT FROM AUTHOR]

Vernonia amygdalina leaves were investigated for their histochemical properties and antidiabetic activities. Histochemical analysis of the leaf revealed distributions of acidic lipid, mucilage, and pectin, lipids, polyphenols, and alkaloids at the mid rib, glandular trichome, and epidermis. HPLC analysis of the leaves hot water infusion revealed the presence of quercetin and (‐)‐epi‐catechin. The infusion had significant (p < 0.05) 2,2′‐diphenyl‐1‐picrylhydrazyl scavenging activity and ferric reducing antioxidant power. Ex vivo antioxidative analysis revealed the ability of the infusion to increase glutathione level, superoxide dismutase, and catalase activities, while concomitantly depleting malondialdehyde level and DNA fragmentation in Fe2+‐induced hepatic injury. The infusion showed significant (p < 0.05) inhibitory activity against α‐glucosidase and pancreatic lipase. It also inhibited intestinal glucose absorption and enhanced muscle glucose uptake, respectively. The ability of the infusion to abate oxidative stress, DNA fragmentation and stimulate muscle glucose uptake may suggest the antioxidative, anti‐apoptotic, and insulin‐sensitizing activity of V. amygdalina. Practical applications: Vernonia amygdalina (bitter leaf) is among the common leafy vegetables in West Africa reported for its various medicinal and nutritional properties. It is utilized as a food ingredient as well as supplement for the treatment and management of type 2 diabetes (T2D). Its ability to inhibit intestinal glucose absorption, enhance muscle glucose uptake, and protect against hepatic oxidative stress gives more credence to its reported antidiabetic properties. Being a common leafy vegetable, V. amygdalina can be a cheap source of nutraceutical for the treatment and management of T2D and its complications. [ABSTRACT FROM AUTHOR]

The antioxidative and antidiabetic effects of the aqueous extract of Phaseolus lunatus were investigated in vitro and ex vivo. The seeds were subjected to aqueous extraction, after defatting with n‐hexane. The extract (15, 30, 60, 120, 240 µg/ml) showed significant (p < 0.05) free radical scavenging and enzyme inhibitory activities in vitro. It significantly (p < 0.05) elevated glutathione level with concomitant depletion of malondialdehyde level as well as increased superoxide dismutase and catalase activities in rat liver. Fe2+‐induced hepatic DNA fragmentation was also significantly (p < 0.05) suppressed. The extract significantly inhibited intestinal glucose absorption and increased muscle glucose uptake with and without insulin. The inhibitory activities and reversion of hepatic redox imbalance, as well as inhibition of intestinal glucose absorption and increased muscle glucose uptake by P. lunatus suggest an antihyperglycemic and antioxidative effect. These can be ascribed to the synergistic effect of the phytochemicals and amino acids identified in the extract. Practical applications: Lima beans (Phaseolus lunatus) is among the many underutilized legumes with reported nutritional benefits. It is utilized locally in Nigeria in treating and managing diabetes and its complications, but without any scientific proof. The ability of the legume to inhibit digestive enzymes linked to postprandial blood glucose spike, as well as inhibition of intestinal glucose absorption and increased muscle glucose uptake substantiates its antidiabetic folkloric uses. The amino acid constituents also indicate its nutritional properties. These findings will promote its utilization not only as an antidiabetic functional food but also as a nutritional meal. [ABSTRACT FROM AUTHOR]