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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]

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]

Prostate cancer is still one of the world's top triggers of mortality. In light of the restricted therapy choices for people with prostate cancer, natural substance-based prevention and therapeutic techniques can contribute significantly to combating this illness.P. africana, a Rosaceae-family evergreen shrub native to Sub-Saharan Africa, has traditionally been used to cure prostate cancer. The focus of this research was therefore to review the phytochemistry of P. africana against prostate cancer. P. africana extracts produced from various plant sections have been reported to constitute a number of phytochemical components. Triterpenoids, phenols, sterols, and fatty acids are the most important. In vitro and in vivo experiments have shown that phytochemicals obtained from P. africana have antiprostate cancer characteristics. P. africana extracts have been shown to have powerful antiangiogenic and antiandrogenic properties, which have been partly attributed to synergistic effects of the constituent compounds. The extracts exert anticancer effect in prostate cancer cells by inducing apoptosis, inhibiting cell growth and proliferation, and suppressing signaling factors that promotes invasion, migration, and metastasis of cancer cells. Although, further preclinical and clinical studies are still needed to provide a more reliable scientific validation on the use of P. africana in cancer treatment. The qualitative synthesis from this review provides an evidence-based platform that will stimulate future studies, with prospects of developing safe, affordable, and effective pharmaceuticals for treating prostate cancer. [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]

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]

Pomegranate peel contains ellagitannins as antioxidant principles but the aqueous extraction temperature for optimum ellagitannins recovery and antioxidant profile remains elusive. This study employed advanced chemometrics models, including principal component analysis (PCA) and orthogonal projections to latent structures (OPLS) to determine the influence of different extraction temperatures (25–95 °C) during a 1 h period on the antioxidant profile of the peel's aqueous extract, as well as the profile of the constituent ellagitannins recovered using Amberlite® XAD16N resin and characterized by LC–MS. Extraction at 78 °C had the most potent radical scavenging potency, oxygen radical absorbance capacity (ORAC), and anti-lipid peroxidative activity, which was consistent with its highest ellagitannins constituents relative to other extraction temperatures. Pearson's bivariate correlation depicted strong positive correlations (r = 0.7–0.9) between the ellagitannins and the anti-lipid peroxidative profile of the extracts. PCA and OPLS models adequately characterized and predicted the variation and patterns in the antioxidant and phytochemical datasets (up to 93.6%). OPLS biplot showed a distinct clustering pattern of the antioxidant and ellagitannins variables around 78 °C extraction temperature, suggesting the observable influence of the ellagitannins on the potent antioxidant profile of the 78 °C extraction. The variable contribution plots, as well as the obtained antioxidant data, suggest punicalagins, granatin A, and ellagic acid as notable influencing ellagitannins. It is safe to speculate that extraction at 78 °C optimally influenced the ellagitannins and antioxidant profile of pomegranate fruit peel. Thus, this aqueous extraction temperature may be promising for optimally recovering the ellagitannins from pomegranate peel, without sacrificing the antioxidant capacity. [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]

Graphical abstract Highlights • Azadirachta indica stembark ethanol fraction scavenges free radicals and improves oxidative enzyme in hepatic tissue. • Its polyphenols inhibit carbohydrate digesting enzymes activity and improve glucose uptake in muscle. • The in silico studies between the bioactive compounds and the carbohydrate metabolizing enzymes show a positive interactions. • This result validate the folkloric use of A. indica stem bark in the management of diabetes. Abstract The progression of secondary complications in type 2 diabetes (T2D) has been linked to oxidative stress caused by hyperglycemia. Therefore, the control of hyperglycemia is the main target in the treatment of diabetes. The present study investigated the scavenging and ameliorative potentials of different fractions of Azadirachta indica (A. indica) ethanol stem bark extract in Fe2+-induced oxidative injury in hepatic tissue as well as their ability to inhibit enzymes linked to diabetes and in enhancing muscle glucose uptake via some in vitro and ex vivo experimental models. The results revealed that the butanol fraction of the extract showed a significantly (p < 0.05) higher DPPH scavenging activity than the other fractions (IC 50 0.0154 μg/mL), while the aqueous fraction showed the highest FRAP activity (IC 50 25.32 μg/mL). Although all the fractions ameliorated Fe2+-induced oxidative injury in hepatic tissue by significantly reducing malondialdehyde (MDA) concentration in a dose dependent manner, the butanol fraction showed the highest activity in this regard. In addition, the activities of catalase and superoxide dismutase (SOD) were significantly improved by the butanol and dichloromethane fractions. Butanol and ethyl acetate fractions showed the highest inhibitory effect on α-glucosidase (IC 50 0.23 μg/mL) and α-amylase (IC 50 14.79 μg/mL) activities, respectively. Although all the fractions significantly improved glucose uptake in psoas muscle with or without insulin, the butanol fraction showed the highest activity (GU 50 6.22 μg/mL) in this regard. Gas chromatography–mass spectroscopy (GC–MS) analysis of the fractions revealed the presence of sistosterol, stigmasterol, campestrol, squalene, nimbiol among others. Molecular docking of some of these compounds with AMP-activated protein kinase (α-AMPK), α-amylase and α-glucosidase showed a positive interaction. These results suggest that the butanol and ethyl acetate fractions of A. indica may have bioactive compounds with antidiabetic potentials. [ABSTRACT FROM AUTHOR]

The present study investigated the in vitro and ex vivo antioxidant, anti-diabetic and anti-obesogenic potentials of different solvent (ethyl acetate, ethanol and water) extracts from the aerial parts of Boerhaavia diffusa . The ferric reducing antioxidant power (FRAP), DPPH scavenging activity and the ameliorative effects of the extracts on Fe 2+ -induced oxidative injury was investigated both in vitro and ex vivo. Alpha glucosidase and pancreatic lipase inhibitory potentials of the extracts were examined in vitro , while the effects of the ethanol extract on abdominal glucose intake and muscle glucose uptake were determined in freshly harvested tissues ex vivo. The extracts were subjected to Gas Chromatography-Mass Spectrometry (GC–MS) analysis to identify their possible bioactive components. The ethanol extract showed the most potent FRAP and DPPH radical scavenging activities compared to other extracts. All extracts increased catalase and SOD activities, and GSH levels in oxidative pancreatic injury. Both ethanol and aqueous extracts exhibited remarkable enzyme inhibitory activities, which was significantly higher than ethyl acetate extract and acarbose but was not comparable to orlistat. The ethanol extract portrayed a dose-dependent inhibitory effect on jejunal glucose uptake and enhancement of muscle glucose uptake. 9-(4 methoxyphenyl) xanthene, xanthone and stigmasterol showed strong binding affinities for α-glucosidase and lipase enzymes tested. Data from this study suggest that aerial parts of B. diffusa (particularly the ethanol extract) may not only exhibit antioxidant potentials but may also mediate anti-lipidemic and anti-hyperglycemic effects via inhibiting fat and carbohydrate digestion as well as abdominal glucose intake and enhancing muscle glucose uptake. [ABSTRACT FROM AUTHOR]

Ellagitannins are the predominant bioactive tannins present in the peel of pomegranate. Studies have explored different extraction solvents to maximize recovery of the bioactive phytochemicals in pomegranate peel but lack proper statistical correlation between the extraction solvent, phytochemistry and bioactivity. This study employed advanced chemometrics models, including principal component analysis (PCA) and orthogonal projections to latent structures (OPLS) in determining the solvent extraction (among methanol, ethanol, acetone and water) that will yield optimum antioxidant and ellagitannins profiles from "Wonderful" pomegranate peel. Acetone extraction had the highest (p ˂ 0.05) total phenol (TFC) and flavonoid contents and strongest (p ˂ 0.05) Fe3+ reducing effect, while methanol extraction had the strongest (p ˂ 0.05) radical scavenging activity. The oxygen radical absorbance capacity (ORAC) and anti-lipid peroxidative activities of both solvent extractions outperformed that of the ethanol and water extractions. Tannins purified using Amberlite® XAD16N resin were highest for acetone and methanol extractions. LCMS-quantified ellagitannins in the tannins varied for the different extractions. PCA and OPLS models adequately characterized, described and predicted the variation and patterns in the antioxidant and ellagitannins datasets (up to 95% for PCA). OPLS bi-plot showed that the high ellagic acid constituents and total tannins yield of the methanol extraction influenced its potent radical scavenging activity, while the ellagitannin constituents including punicalagins, granatin A, geraniin and casuarinin influenced the high TFC, as well as the potent Fe3+ reducing, ORAC and anti-lipid peroxidative activities of acetone extraction. Acetone and methanol extraction of pomegranate peel are promising for optimum ellagitannins recovery and antioxidant profile. [ABSTRACT FROM AUTHOR]

Targeting oxidative stress and inflammatory signaling pathways is an effective cancer prevention and therapy approach. The mechanism of action of synthesized salicylidene-based compounds was investigated in regulating key molecular targets of breast cancer development. Compounds (1), (4), (5), and (7) were found to be more cytotoxic to MCF-7 and 4T1 cells compared to non-cancerous Chang liver cells, while these compounds were cytotoxic to MDA-MB-231 cells, but with poor selectivity. The colony formation assay indicated that bioactive compounds induced significant damage to breast cancer cells, as observed by a reduction in the number of colonies compared to control cells. By inducing a concentration and time-dependent increase of luminescence and fluorescence of phosphatidylserine, and activating the expression of caspases-3, -7, -8, -9 in breast cancer cells, (1) and (7) have shown to induce caspase-dependent apoptosis. The downregulation of NF-kB-p65 and an upregulation of TP53 expression after exposure to bioactive compounds, demonstrated the suppression of two key targets of breast cancer development. Molecular docking studies revealed that selected protein targets strongly interact with bioactive compounds, and the estimated inhibition constants (Ki) of JAK2, STAT3, COX-2, HPV31 E6, EGFR1, TP53, and PARP1 were significantly decreased compared to acetylsalicylic acid. This could be a clear indication that these protein targets are implicated with antiproliferative efficacy, thereby warranting the potential of (1) and (7) to be used as anti-breast cancer drug candidates. [Display omitted] [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]

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]

Raffia palm (Raphia hookeri G. Mann & H. Wendl) wine (RPW) is a natural beverage obtained from the R. hookeri consumed for refreshment and medicinal purposes. For medicinal purposes, it is used singly or as macerating agent for other medicinal plants for the treatment of several diseases. This study investigates the effect of Raffia palm wine on dysregulated lipid metabolic pathways in testicular tissues of type 2 diabetic (T2D) rats. Raffia palm wine (150 and 300 mg/kg bodyweight) was administered to two T2D groups respectively, another T2D group was not administered treatment and served as negative control, while metformin served as the standard drug. After 6 weeks of treatment, the rats were sacrificed, and the testes collected. After weighing, the organs were homogenized in 20% methanol/ethanol and centrifuged at 20,000 g to extract the lipid metabolites. GC-MS analysis of the supernatants revealed an alteration of the metabolites on induction of T2D, with concomitant generation of 10 metabolites. Raffia palm wine inhibited the T2D-generated metabolites while replenishing cholesterol and squalene levels, with concomitant generation of 7 and 8 metabolites for low and high dose treatment respectively. Pathway enrichment analysis of the metabolites revealed a decreased level of steroid biosynthesis and increased level of fatty acid biosynthesis. Raffia palm wine inactivated glycerolipid, fatty acid, and arachidonic acid metabolisms, fatty acid biosynthesis and fatty acid elongation in mitochondria pathways, and activated pathways for plasmalogen synthesis, mitochondrial beta-oxidation of long chain saturated fatty acids. The replenishment and generation of these metabolites and additional ones as well as activation of pathways involved in energy generation, phospholipids, antioxidant activity, steroidogenesis and spermatogenesis suggest a therapeutic effect of Raffia palm wine against hyperglycemic-induced testicular dysfunction. [Display omitted] • Induction of type 2 diabetes caused alterations in testicular lipid metabolites. • Lipid metabolic pathways were altered in testes of type 2 diabetic rats. • Treatment with raffia palm wine suppressed these alterations. [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]

The antioxidant and anti-proinflammatory activities of l-leucine were investigated on oxidative testicular injury, ex vivo. In vitro analysis revealed l-leucine to be a potent scavenger of free radicals, while inhibiting acetylcholinesterase activity. Oxidative injury was induced in testicular tissues using FeSO4. Treatment with l-leucine led to depletion of oxidative-induced elevated levels of NO, MDA, and myeloperoxidase activity, with concomitant elevation of reduced glutathione and non-protein thiol levels, SOD and catalase activities. l-leucine caused a significant (p < 0.05) alteration of oxidative-elevated acetylcholinesterase and chymotrypsin activities, while concomitantly elevating the activities of ATPase, ENTPDase and 5′-nucleotidase. l-leucine conferred a protective effect against oxidative induced DNA damage. Molecular docking revealed molecular interactions with COX-2, IL-1 beta and iNOS. Treatment with l-leucine led to restoration of oxidative depleted ascorbic acid-2-sulfate, with concomitant depletion of the oxidative induced metabolites: D-4-Hydroxy-2-oxoglutarate, l-cystine, adenosine triphosphate, maleylacetoacetic acid, cholesteryl ester, and 6-Hydroxy flavin adenine dinucleotide. Treatment with l-leucine reactivated glycolysis while concomitantly deactivating oxidative-induced citrate cycle and increasing the impact-fold of purine metabolism pathway. l-leucine was predicted not to be an inhibitor of CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4, with a predicted LD50 value of 5000 mg/Kg and toxicity class of 5. Additionally, l-leucine showed little or no in vitro cytotoxicity in mammalian cells. These results suggest the therapeutic potentials of l-leucine on oxidative testicular injury, as evident by its ability to attenuate oxidative stress and proinflammation, while stalling cholinergic dysfunction and modulating nucleotide hyrolysis; as well as modulate oxidative dysregulated metabolites and their pathways. [ABSTRACT FROM AUTHOR]

Dacryodes edulis L. is an evergreen tree indigenous to western and eastern Africa which is utilized for nutritional and medicinal purposes. Folklorically, different parts of the tree are used in treating and managing diabetes and its complications. The antidiabetic effect of the butanol fraction of D. edulis ethanol extract (BFDE) was studied in fructose-streptozotocin induced type 2 diabetic rats. The ethanol extract was fractionated to yield the hexane, dichloromethane, ethyl acetate, butanol and aqueous fractions. The in vitro antidiabetic activities of the fractions were determined by their ability to inhibit α-glucosidase activity. BDFE was the most active and showed no cytotoxic effect while stimulating glucose uptake in 3T3-L1 adipocytes. Thus, selected for in vivo study. Diabetic rats were grouped into 4. The negative control group was administered water only, another group was treated with metformin (200 mg/kg bodyweight), while the other groups were administered BDFE at 150 and 300 mg/kg bodyweight respectively. Two other groups consisting of normal rats were given water and BFDE (300 mg/kg bodyweight) respectively, with the former serving as normal control. After 6 weeks of intervention, the rats were humanely sacrificed using appropriate anaesthesia. Treatment with the fraction significantly (p < 0.05) reduced the blood glucose level of the diabetic rats, with concomitant increase in serum insulin secretion. It also caused significant (p < 0.05) elevation of reduced glutathione level, superoxide dismutase, catalase, α-amylase, and ATPase activities, with concomitant depletion in myeloperoxidase activity, NO and MDA levels of the serum and pancreas. The pancreatic morphology and β-cell function were significantly improved in BFDE-treated rats, with restoration of the pancreatic capillary networks. Treatment with BFDE significantly (p < 0.05) inhibited the activities of glycogen phosphorylase, fructose 1,6 biphosphatase, glucose 6 phosphatase, and acetylcholinesterase, while suppressing the expression of Nrf2. HPLC analysis revealed the presence of gallic acid, vanillic acid, vanillin, and (−)-epicatechin in the fraction. These results portray the antidiabetic and antioxidative properties of BFDE, which may be a synergistic consequence of the identified phenolics. Image 1 [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]

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]

Raffia palm (Raphia hookeri) wine (RPW) is amongst the natural products from plants, utilized singly or in combination with other medicinal plants for the treatment of several ailments including Diabetes Mellitus (DM). However, there is a scientific dearth on its antidiabetic activity. The antidiabetic effect of RPW and its possible mechanism of actions were investigated in diabetic rats. Four groups of male SD rats were first supplied with 10% fructose solution ad libitum for 2 weeks instead of drinking water followed by an intraperitonial injection of streptozotocin (40 mg/kg) to induce diabetes. Two diabetic groups were administered RPW at 150 and 300 mg/kg bodyweight (BW) respectively; a group was administered with metformin, while the other one was served as a negative control. Two groups of normal rats were administered with water and RPW (300 mg/kg BW) and served as normal control and normal toxicology group, respectively. Five weeks treatment of RPW led to significant (p < 0.05) increase in serum insulin and HDL-c levels with concomitant reduction in blood glucose, fructosamine, ALT, uric acid, triglycerides and LDL-c levels in diabetic rats. Rats treated with RPW had elevated levels of GSH, SOD, catalase, ATPase and α-amylase activities, while reduced NO level and myeloperoxidase activity was observed in their serum and pancreatic tissues. RPW also improved pancreatic β-cell function and restored β- and acinar cells morphology, and capillary networks. The activities of glycogen phosphorylase, fructose 1,6 biphosphatase, glucose-6-phosphatase, and acetylcholinesterase were also inhibited in RPW-treated diabetic rats, with concomitant down regulation of Nrf2 gene expression. The data of this study suggest that RPW modulates glucose homeostasis by enhancing insulin secretion as well as inhibiting redox imbalance in diabetic rats, which may be attributed to the synergetic effects of its phytochemical constituents as identified by GC-MS analysis. Image 1 [ABSTRACT FROM AUTHOR]

The therapeutic effect of the hot water infusion of Cola nitida against hyperglycemia-induced neurotoxicity, cerebellar neurodegeneration and elemental deregulations was investigated in fructose-streptozotocin induced rat model of type 2 diabetes (T2D). A diabetic group was administered drinking water, two other diabetic groups were treated with C. nitida at 150 and 300 mg/kg bodyweight respectively, while another group was administered metformin (200 mg/kg bodyweight). Two other groups consisting of normal rats, were administered drinking water and C. nitida (300 mg/kg bodyweight). After 6 weeks of treatment, their brains were collected. Treatment with C. nitida led to suppression of oxidative stress, significantly elevating reduced glutathione (GSH) levels, superoxide dismutase and catalase activities, concomitant with depletion of malondialdehyde (MDA) levels. Acetylcholinesterase and ATPase activities were significantly inhibited in C. nitida -treated diabetic rats. Histological and microscopic analysis also revealed a restorative effect of C. nitida on T2D-altered distribution of elements, neurons and axonal nodes. Treatment with C. nitida also led to significant inhibition of Nrf2 expression in the cerebellar cortex. These results suggest the therapeutic effects of C. nitida in maintenance of the neuronal integrity and antioxidant status of the brain in T2D. These neuroprotective activities can be attributed to the identified alkaloid, caffeine in the infusion. • Cola nitida suppressed oxidative stress biomarkers and enzyme activities in brain tissues of type 2 diabetic rats. • Cola nitida inhibited cholinesterase and ATPase activities in brain tissues of type 2 diabetic rats. • Cola nitida restored morphological changes in cerebellar cortices of type 2 diabetic rats. • Cola nitida suppressed the expression of nrf2 in cerebellar cortices of type 2 diabetic rats. [ABSTRACT FROM AUTHOR]

Cola nitida (Vent.) Schott & Endl. are among the common medicinal plants employed in traditional medicine for treating diabetes and its complications. The present study investigated the effect of Cola nitida infusion on the expression of key genes involved in insulin signaling vis-à-vis Insulin receptor substrate 1 (IRS-1), tumor protein P53 gene, glucose transporter type 4 (GLUT4), phosphoinositide 3-kinases (PI3K) and B-cell lymphoma-2 (BCL2) in skeletal muscles of type 2 diabetic (T2D) rats. Type 2 diabetic rats were administered C. nitida infusion at low and high doses (150 and 300 mg/kg bodyweight, respectively), while a high dose of the infusion was also administered to a normal toxicological group. Metformin served as the standard antidiabetic drug. The rats were sacrificed at the end of the experimental period. Their psoas muscles were harvested and assayed for the expressions of IRS1, p53, GLUT4, PI3K and BCL2. The studied genes were further subjected to enrichment analysis using the ShinyGO 0.76 online software. Induction of T2D upregulated the expressions of IRS-1, p53, PI3K and BCL2 in psoas muscles, while concomitantly downregulating GLUT4 expression. These expressions were significantly reversed in type 2 diabetic rats treated with C. nitida infusion, and the results were statistically significant compared to metformin. Gene enrichment analysis revealed that the genes were linked to intrinsic pathways and biological processes involved in insulin resistance. The infusion further improved muscle glucose uptake, ex vivo. Molecular docking and molecular dynamics stimulation of C. nitida infusion phytoconstituents, caffeine and theobromine with IRS-1, p53, GLUT4, PI3K and BCL2 revealed a strong binding affinity as evident by the RMSD and RMSF values. These results indicate the potentials of C. nitida infusion to improve glucose homeostasis in skeletal muscles of type 2 diabetic rats. [Display omitted] • Induction of type 2 diabetes upregulated the expressions of IRS-1, p53, PI3K and BCL2 in psoas musclesn. • Treatment with C. nitida revised these expressions. • Gene enrichment analysis revealed the genes were linked to biological processes involved in insulin resistance. • Cola nitida improved muscle glucose uptake, ex vivo. • Molecular dynamics stimulation revealed a strong affinity of C. nitida phytoconstituents with IRS-1, P53, GLUT4, PI3K and BCL2. [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]

There have been increasing interest in the use of plant-derived substance as immunomodulators for the treatment and management of inflammatory ailments. Clerodendrum volubile , a leafy vegetable is known for its folkloric applications in the treatments of several inflammatory related ailments, but with little scientific evidence. This study reports the isolation, structure elucidation and in vitro immunomodulatory potentials of pectolinarigenin from C. volubile leaves. The immunomodulatory potentials of the crude methanolic extract and fractions [ n -hexane (Hex), dichloromethane (DCM), ethyl acetate (EtOAc) and n − butanol (BuOH)] were investigated on whole blood, neutrophil and macrophage phagocytic respiratory burst using luminol-amplified chemiluminescence technique. DCM fraction showed higher inhibitory activity on respiratory burst, indicating high suppressive immunomodulatory potency. The DCM fraction was further fractionated using a gravity column chromatography loaded with silica gel. The column was eluted with mixtures of Hex and DCM (92.5:7.5) in increasing order of polarity up to Hex: DCM (88:12) to afford 5,7-Dihydroxy-6,4′-dimethoxyflavone (pectolinarigenin). The structure of the compound was established using data obtained from 1 H- and 13 C NMR spectroscopies and mass spectrometry. The isolated flavone was investigated for its inhibitory activity of neutrophil phagocytes respiratory burst as well as T − Cell proliferation. The compound exhibited significant activities (at p < 0.05) indicating high suppressive immunomodulatory potency. The potent suppressive effect of pectolinarigenin on polymorphonuclear neutrophils (PMNs) respiratory oxidative burst and T − cell proliferation suggests an immunomodulatory potential and pathway of the flavonoid. [ABSTRACT FROM AUTHOR]

Recently the complexation-mediated antioxidative and glycaemic control synergism between zinc(II) and caffeic acid was demonstrated in vitro. The present study evaluated the complexation-mediated antidiabetic and antioxidative synergism between zinc(II) and caffeic acid in diabetic rats and the possible underlying mechanisms. Male SD rats were induced with diabetes using 10% fructose and 40 mg/kg bw streptozotocin. The diabetic rats were treated with Zn(II)-caffeic acid complex and its precursors (caffeic acid and zinc acetate) for 4 weeks at predetermined doses. The effect of the treatments on diabetes and oxidative stress was measured. The complex ameliorated diabetic alterations. It reduced polyphagia and polydipsia and recovered weight loss. It increased insulin secretion, insulin sensitivity, hepatic and muscle glycogen, muscle hexokinase activity and Akt phosphorylation, which resulted in improved glucose tolerance and reduced blood glucose in the diabetic rats. The complex concomitantly reduced systemic and tissue lipid peroxidation and increased antioxidant enzymes activity in the diabetic rats. The complex outperformed the antidiabetic and antioxidative action of its precursors and had a broader bioactivity profile. Complexing zinc acetate with caffeic acid improved their ameliorative effect on insulin resistance by ∼24% and 42%, respectively, as well as their anti-hyperglycaemic action by ∼24 – 36% and ∼42 – 47%, respectively, suggesting a complexation-mediated synergism. In some instances, the antidiabetic action of the complex was comparable to metformin, while its antioxidant effect was better than that of metformin. Zinc(II)-caffeic acid complexation may be an alternative approach to improving the efficacy of antidiabetic and antioxidative therapy with minimal adverse or side effects. [Display omitted] [ABSTRACT FROM AUTHOR]

The immunomodulatory potentials of the crude methanolic extract and fractions [n-hexane (Hex), n-dichloromethane (DCM), ethyl acetate (EtOAc) and n–butanol (BuOH)] of Clerodendrum volubile flowers were investigated on whole blood phagocytic oxidative burst using luminol-amplified chemiluminescence technique. They were also investigated for their free radicals scavenging activities. The DCM fraction showed significant (p < 0.05) anti-oxidative burst and free radical scavenging activities indicating high immunomodulatory and antioxidant potencies respectively. Cytotoxicity assay of the DCM fraction revealed a cytotoxic effect on CC-1 normal cell line. GCMS analysis revealed the presence of triacetin; 3,6-dimethyl-3-octanol; 2R – Acetoxymethyl-1,3,3–trimethtyl – 4 t – (3-methyl-2-buten-1-yl) – 1c – cyclohexanol and Stigmastan – 3,5–diene in DCM fraction. These compounds were docked with the active sites of cyclooxygenase-2 (COX-2). Triacetin, 3,6-dimethyl-3-Octanol, and 2R-Acetoxymethyl-1,3,3-trimethtyl-4t-(3-methyl-2-buten-1-yl)-1c-cyclohexanol docked comfortably with COX-2 with good scoring function (-CDocker energy) indicating their inhibitory potency against COX-2. 3,6–dimethyl-3- O ctanol, displayed the lowest predicted free energy of binding (−21.4 kcal mol −1 ) suggesting its stronger interaction with COX-2, this was followed by 2R – Acetoxymethyl-1, 3, 3-trimethtyl-4t-(3-methyl-2-buten-1-yl)-1c-cyclhexanol (BE = −20.5 kcal mol −1 ), and triacetin (BE = −10.9 kcal mol −1 ). Stigmastan – 3,5–diene failed to dock with COX-2. The observed suppressive effect of the DCM fraction of C. volubile flower methanolic extract on phagocytic oxidative burst indicates an immunomodulatory potential. This is further reflected in its free scavenging activities and synergetic modulation of COX-2 activities by its identified compounds in silico . [ABSTRACT FROM AUTHOR]

Zinc and syringic acid have metabolic and antioxidant medicinal potentials. A novel zinc(II)–syringic acid complex with improved anti-hyperglycaemic and antioxidant potential was developed. Zinc(II) was complexed with syringic acid in a 1:2 molar ratio and characterized using FT-IR, 1H NMR and LC-MS. Different experimental models were used to compare the anti-hyperglycaemic and antioxidant properties between the complex and precursors. A Zn(II)-bisyringate.2H 2 O complex was formed. The in vitro radical scavenging and Fe3+ reducing antioxidant, antiglycation, and α-glucosidase inhibitory activities of the complex were 1.8–5.2 folds stronger than those of the syringic acid precursor and comparable to those of the positive controls. The complex possessed an increased ability to inhibit lipid peroxidation (by 1.6–1.7 folds) and glutathione depletion (2.8–3 folds) relative to syringic acid in Chang liver cells and liver tissues isolated from rats. The complex exhibited a higher glucose uptake effect (EC 50 = 20.4 and 386 µM) than its precursors (EC 50 = 71.1 and 6460 µM) in L6-myotubes and psoas muscle tissues isolated from rats, respectively, which may be linked to the observed increased cellular zinc uptake potentiated by complexation. Tissue glucose uptake activity was accompanied by increased hexokinase activity, suggesting increased glucose utilization. Moreover, treatment increased tissue phospho-Akt/pan-Akt ratio. The complex had strong molecular docking scores than syringic acid with target proteins linked to diabetes. The presence of two syringic acid moieties and Zn(II) in the complex influenced its potency. The complex was not hepatotoxic and myotoxic in vitro. Zinc-syringic acid complexation may be a novel promising therapeutic approach for diabetes and oxidative complications. [Display omitted] [ABSTRACT FROM AUTHOR]

Cannabis sativa L. is among numerous medicinal plants widely used in traditional medicine in treating various ailments including kidney diseases. The protective effect of C. sativa on oxidative stress, cholinergic and purinergic dysfunctions, and dysregulated glucogenic activities were investigated in oxidative injured kidney (Vero) cell lines. Fixed Vero cells were treated with sequential extracts (hexane, dichloromethane [DCM] and ethanol) of C. sativa leaves for 48 h before subjecting to MTT assay. Vero cells were further incubated with FeSO 4 for 30 min, following pretreatment with C. sativa extracts for 25 min. Normal control consisted of Vero cells not treated with the extracts and/or FeSO 4 , while untreated (negative) control consisted of cells treated with only FeSO 4. MTT assay revealed the extracts were slightly cytotoxic at the highest concentrations (250 μg/mL). There was a significant depletion in glutathione level and catalase activity on induction of oxidative stress, with significant elevation in malondialdehyde level, acetylcholinesterase, ATPase, ENTPDase, fructose-1,6-biphosphatase, glucose 6-phosphatase and glycogen phosphorylase activities. These activities and levels were significantly reversed following pretreatment with C. sativa extracts. These results portray the protective potentials of C. sativa against iron-mediated oxidative renal injury as depicted by the ability of its extracts to mitigate redox imbalance and suppress acetylcholinestererase activity, while concomitantly modulating purinergic and glucogenic enzymes activities in Vero cells. [Display omitted] • Cannabis sativa had no significant effect on the proliferation of Vero cells. • Cannabis sativa mitigated oxidative stress in oxidative injured Vero cells. • Cannabis sativa modulated cholinergic activities in oxidative injured Vero cells. • Cannabis sativa modulated purinergic activities in oxidative injured Vero cells. • Cannabis sativa suppressed glucogenic activities in oxidative injured Vero cells. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Bridelia ferruginea Benth. (Euphorbiaceae) is among the medicinal plants commonly used for the management of type 2 diabetes (T2D) and its complications. The hepato-therapeutic effect of the butanol fraction of Bridelia ferruginea leaves was investigated in diabetic rats. The butanol fraction of B. ferruginea was given to type 2 diabetic rats at both low and high doses (150 and 300 mg/kg bodyweight, respectively), while metformin and glibenclamide served as the standard anti-diabetic drugs. A normal toxicological group was administered a high dose of the fraction. At the end of the experimental period, the rats were sacrificed, and their livers and psoas muscle collected. The liver was assayed for oxidative stress markers, liver glycogen content, lipid metabolite profile (using GC-MS) and their metabolic pathways were analyzed using the MetaboAnalyst 5.0 online server. The expression of GLUT4 was also assayed in the liver and muscle as well as the identification of signaling pathways associated with GLUT4 expression using the Enrichr online server. In silico molecular docking was used to investigate the molecular interactions of some postulated compound found in B. ferruginea with GLUT4. The ability of the fraction to stimulate muscle glucose uptake was determined in isolated rat psoas muscle ex vivo. Treatment with the high dose of fraction caused an inhibition of lipid peroxidation as well as the elevation of catalase, SOD, glutathione reductase and glutathione peroxidase activities in the rat liver. There was an increased expression of GLUT4 in livers and muscles of diabetic rats following treatment with B. ferruginea. Treatment with the fraction also caused inactivation of diabetes-activated pathways and changes in the distribution of the hepatic lipid metabolites. Molecular docking analysis revealed strong molecular interactions of pyrogallol and sitosterol with GLUT4. These data illustrate the hepato-protective effect of B. ferruginea in diabetic rats which compare favorably with the tested anti-diabetic drugs (metformin and glibenclamide). [Display omitted] [ABSTRACT FROM AUTHOR]

Cola nitida is amongst the evergreen plants native to West Africa used in the treatment of various ailments including diabetes. Aim of the study : This study aims to investigate the antidiabetic effects of the hot water extract of C. nitida seeds in type 2 diabetic rats. Type 2 diabetic rats were orally administered with low (150 mg/kg bw) and high (300 mg/kg bw) doses of the hot water extract for 6 wk and thereafter, blood glucose, insulin level, lipid profile, pancreatic β-cell function, perfusion and morphology, redox imbalance, glycolytic and cholinergic enzymes, as well as of caspase-3 and Nrf2 expressions were measured. Treatment with the extract led to significant depletion of blood glucose, serum triglycerides, LDL-cholesterol, fructosamine, ALT, and uric acids, while elevating serum insulin and HDL-cholesterol levels. The infusion also significantly (p < 0.05) elevated GSH level, SOD, catalase, α-amylase, and ATPase activities, with concomitant depletion of myeloperoxidase enzyme activity, and NO and MDA levels in the serum and pancreas. Significantly (p < 0.05) improved pancreatic β-cell function and morphology were observed in rats treated with C. nitida , with restored pancreatic capillary networks. C. nitida inhibited the activities of glycogen phosphorylase, fructose 1,6 biphosphatase, glucose 6 phosphatase, and acetylcholinesterase while downregulated the Nrf2 expression. NMR analysis of the extract revealed the presence of caffeine and theobromine. The molecular docking studies indicated that identified compounds displayed strong molecular interactions with caspase-3 and Nrf2. These results insinuate the antidiabetic activities of C. nitida hot water extract and may be attributed to the NMR-identified compounds. Image 1 [ABSTRACT FROM AUTHOR]