Search

John Oludele Olanlokun,1 Mercy Toluwase Ekundayo,1 Oluwakemi Ebenezer,2 Neil Anthony Koorbanally,2 Olufunso Olabode Olorunsogo1 1Laboratories for Biomembrane Research and Biotechnology, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, 4000, Nigeria; 2School of Chemistry and Physics, University of KwaZulu-Natal, Durban, 4006, South AfricaCorrespondence: John Oludele OlanlokunDepartment of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Room NB 305, Ibadan, NigeriaEmail jodel72000@yahoo.comIntroduction: Resistant malaria is a fatal disease. Globimetula braunii (African Mistletoe) is traditionally used for malarial treatment but this fact has not been scientifically reported.Methods: Plasmodium berghei (NK65)-infected male Swiss mice (20± 2 g) were treated orally and once daily with 100, 200, and 400 mg/kg BW of methanol extract and its respective hexane, dichloromethane and ethyl acetate fractions for 9 days. P-alaxin was used as control drug P. berghei (ANKA)-infected mice were then treated with the most potent fraction for 5 days. Parasitemia and parasite clearance were determined by microscopy, while hematological parameters, heme, hemozoin, and mouse erythrocyte membrane stabilisation were assayed. The phytochemicals in the most potent fraction were identified using gas chromatography-mass spectrometry.Results: Hexane fraction (HF)-treated mice (400 mg/kg BW) had the least mean parasite load (0.00 ± 0.00; 0.14 ± 0.05%) and highest clearance (100 ± 0.00; 75.50 ± 4.95%) compared with infected control (9.81 ± 0.09; 6.84 ± 0.09%) in susceptible and resistant models, respectively. Hexane fraction modulated hematological indices, minimised erythrocyte membrane damage in heat-induced (2.18 ± 0.94%) and hypotonic solution-induced (7.93 ± 0.93%) compared to artequin (5.05 ± 2.18; 6.38 ± 0.33%) and P-alaxin (67.45 ± 5.15; 56.78 ± 1.10%) in both models of membrane stabilisation, respectively. Hexane fraction (P< 0.01) increased heme and decreased hemozoin contents. Friedelan-3-one was identified as the most abundant triterpene.Conclusion: The results indicated that G. braunii has anti-plasmodial properties and minimally dis-stabilised erythrocyte membrane. The major findings in this study are that n-hexane fraction of G. braunii possess excellent and moderate antiplasmodial activity against susceptible and resistant P. berghei, respectively. This was reflected via decreased parasite load, improved hematological parameters, increased heme and decreased hemozoin contents. Friedelan-3-one, a major constituent of the n-hexane fraction, may be responsible for this activity.Keywords: Globimetula braunii, erythrocytes, heme, hemozoin, Plasmodium berghei, resistant malaria

Azadirachta indica A. Juss (Meliaceae) (AI) and Curcuma longa L. (Zingiberaceae) (CL) are used for malaria treatment but their anti-glycolytic and host mitochondrial effects have not been studied. The AI stem-bark and CL rhizomes were extracted with methanol. Methanol extract of CL (Turmeric) was partitioned to yield methanol fraction (MF). Swiss mice infected with Plasmodium berghei (NK 65 strain) were treated with 200 and 400 mg/kg of AI and turmeric for seven days. Turmeric and MF (200 and 400 mg/kg) were combined with 400 mg/kg AI to treat mice infected with Plasmodium berghe i (ANKA strain) for four days. Drug and infected controls mice were treated with artemether lumefantrine (10 mg/kg) and distilled water (10 mL/kg), respectively. Serum lactate dehydrogenase (LDH) and aldolase activities were determined. Liver mitochondria were obtained for mitochondrial permeability transition (mPT) pore opening and F o F 1 ATPase assays. The curcumin content of turmeric was determined using HPLC while LD 50 of Turmeric and AI was also determined. The AI, and its combination with turmeric decreased parasite load and increased chemosuppression in both sensitive and resistant studies while MF and its combinations with AI induced mPT pore opening. In the resistant experiment, AI + Turmeric 400 mg/kg decreased F o F 1 ATPase, LDH and aldolase activities against the infected control. The LD 50 values of both extracts were above 2000 mg/kg while the MF had the highest curcumin content. Antiplasmodial mechanisms of action of AI, CL and their combinations involve anti-glycolytic effects. Their composite formulations are more potent in malaria treatment., Competing Interests: Conflict of interestThe authors declare that there is no conflict of statement., (© Indian Society for Parasitology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Ethnopharmacological Relevance: Andrographis paniculata (AP) ((Burm f.) Wall. ex Nees) is a medicinal plant, documented for its folkloric use in the treatment of malaria., Aim: This study was designed to determine the potency of extract and fractions of A. paniculata (AP) as a curative, both for susceptible and resistant malaria and to also determine the plant's mechanism of action. This study was also designed to determine whether AP extract and its most potent fraction will mitigate infection-mediated mitochondrial dysfunction, and to assess the phytochemical constituents of the most potent fraction., Materials and Methods: n-Hexane, dichloromethane, ethylacetate and methanol were used to partition the methanol extract of A. paniculata. Graded doses of these extract and fractions were used to treat mice infected with chloroquine-sensitive strain of P. berghei in a curative model. The most potent fraction was used to treat mice infected with resistant (ANKA strain) P. berghei. Inhibition of hemozoin formation, reversal of mitochondrial dysfunction and antiinflammatory potentials were determined. A combination of ultraperformance liquid chromatography-quadrupole time of flight-mass spectrometry and nuclear magnetic resonance spectroscopy were used for chemical analysis., Results: Microscopy revealed that the dichloromethane fraction decreased the parasite burden the most, and inhibition of the hemozoin formation is one of its mechanisms of action. The dichloromethane fraction reversed parasite-induced mitochondrial pore opening in the host, enzyme-dependent ATP hydrolysis and peroxidation of host mitochondrial membrane phospholipids as well as its antiinflammatory potentials. The UPLC-qTOF-MS report and NMR fingerprints of the dichloromethane fraction of A. paniculata yielded fourteen compounds of which sibiricinone C was identified from the plant for the first time., Conclusion: Fractions of A. paniculata possess antiplasmodial effects with the dichloromethane fraction having the highest potency. The potent effect of this fraction may be attributed to the phytochemicals present because it contains terpenes implicated with antimalarial and antiinflammatory activities., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests., (Copyright © 2024. Published by Elsevier B.V.)

Plasmodium infection is a health challenge. Although, antiplasmodial drugs kill the parasites, information on the effects of infection and drugs on the expression of some genes is limited. Malaria was induced in two different studies using NK65 (chloroquine-susceptible, study 1), and ANKA (chloroquine-resistant, study 2) strains of Plasmodium berghei in 30 male Swiss mice (n = 5) in each study. Mice orally received 10 mL/kg distilled water, (infected control), Mefloquine (MF) (10 mg/kg), MF and Curcumin (CM) (25 mg/kg), MF and CM (50 mg/kg), CM (25 mg/kg) and CM (50 mg/kg). Five mice (un-infected) were used as the control. After treatment, total Ribonucleic acid (RNA) was isolated from liver and erythrocytes while Deoxyribonucleic acid (DNA)-free RNA were converted to cDNA. Polymerase Chain Reaction (PCR) amplification was performed and relative expressions of FIKK12, AQP3, P38 MAPK, NADH oxidoreductase, and cytochrome oxidase expressions were determined. Markers of glycolysis, toxicity and antioxidants were determined using ELISA assays. While the expression of FIKK12 was blunted by MF in the susceptible study, co-treatment with curcumin (25 mg/kg) yielded the same results in the chloroquine-resistant study. Similar results were obtained on AQP3 in both studies. Curcumin decreased P38 MAPK in both studies. Plasmodium infection decreased NADH oxidoreductase and cytochrome oxidase but mefloquine-curcumin restored the expression of these genes. While glycolysis and toxicity were inhibited, antioxidant systems improved in the treated groups. Curcumin is needed for effective therapeutic efficacy and prevention of toxicity. Plasmodium infection and treatment modulate the expressions of some genes in the host. Curcumin combination with mefloquine modulates the expression of some genes in the host., Competing Interests: Authors declare that no competing interest exists., (© 2024 Published by Elsevier B.V.)

his comprehensive review is designed to evaluate the anticancer properties of β-carbolines derived from medicinal plants, with the ultimate goal of assessing their suitability and potential in cancer treatment, management, and prevention. An exhaustive literature survey was conducted on a wide array of β-carbolines including, but not limited to, harmaline, harmine, harmicine, harman, harmol, harmalol, pinoline, tetrahydroharmine, tryptoline, cordysinin C, cordysinin D, norharmane, and perlolyrine. Various analytical techniques were employed to identify and screen these compounds, followed by a detailed analysis of their anticancer mechanisms. Natural β-carbolines such as harmaline and harmine have shown promising inhibitory effects on the growth of cancer cells, as evidenced by multiple in vitro and in vivo studies. Synthetically derived β-carbolines also displayed noteworthy anticancer, neuroprotective, and cognitive-enhancing effects. The current body of research emphasizes the potential of β-carbolines as a unique source of bioactive compounds for cancer treatment. The diverse range of β-carbolines derived from medicinal plants can offer valuable insights into the development of new therapeutic strategies for cancer management and prevention., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Objective: The effect of Alstonia boonei fractions on glucose homeostasis was investigated via in vitro enzyme inhibition activity, ex vivo glucose uptake assay, and in vivo methods in diabetic rats., Methodology: A. boonei fractions were subjected to in vitro α-glucosidase inhibitory assay and then ex vivo glucose uptake activity. The butanol fraction of the leaves (ABBF) was picked for the in vivo assay since it showed more activity in the initial tests conducted. ABBF was administrated via oral dosing to six-weeks old fructose-fed STZ-induced type 2 diabetic rats over a 5-week experimental period., Results: ABBF treatment at a low dose of 150 mg/kg bw, significantly ( p  < .05) reduced blood glucose level, enhanced oral glucose tolerance ability, restored insulin secretion and hepatic glycogen synthesis as well as promoted islet regeneration than the high dose (300 mg/kg bw)., Conclusion: These results suggest that ABBF could be exploited as a therapeutic potential for treating T2D.

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

The leaves, stem and root bark of Bridelia ferruginea were sequentially extracted with solvents of increasing polarity to yield the hexane, ethyl acetate, ethanol and aqueous extracts. In vitro analysis revealed the ability of the extracts to scavenge 1,1-diphenyl-2-picryl-hydrazyl (DPPH), nitric oxide (NO) and hydroxyl radical. They also inhibited the activities of α -glucosidase, α -amylase and lipase enzymes. Gas chromatography-mass spectroscopic (GC-MS) analysis of the extracts revealed the presence of sterols, aromatics, aliphatic acids and esters. The identified compounds were molecularly docked with α -glucosidase, α -amylase and lipase enzymes. All compounds showed good binding affinities with the enzymes studied. The strongest binding affinities were observed for β -amyrin, 4-phenylbenzophenone and lupenone for α -glucosidase, α -amylase and lipase enzymes, respectively. The data suggest antioxidant and antidiabetic potential of the different parts of B. ferruginea , with the leaves having the highest potential. These properties can be explored for development of novel anti-diabetic drugs.Communicated by Ramaswamy H. Sarma.

Background: Apoptosis is a common pathology in malaria and most antimalarial drugs induce apoptosis during chemotherapy. Globimetula braunii is an African mistletoe used for the treatment of malaria but its effect on mitochondria-mediated apoptosis is not known., Methods: Malarial infection was induced by the intraperitoneal injection of NK 65 strain Plasmodium berghei -infected erythrocytes into mice which were treated with graded doses (100-400 mg/kg) of methanol extract (ME), and fractions of n -hexane, dichloromethane, ethylacetate and methanol (HF, DF, EF and MF) for 9 days after the confirmation of parasitemia. Artequine (10 mg/kg) was used as control drug. The fraction with the highest antiplasmodial activity was used (same dose) to treat mice infected with chloroquine-resistant (ANKA) strain for 5 consecutive days after the confirmation of parasitemia. P-alaxin (10 mg/kg) was used as control drug. On the last day of the treatment, liver mitochondria were isolated and mitochondrial Permeability Transition (mPT) pore opening, mitochondrial F 0 F 1 ATPase (mATPase) activity, lipid peroxidation (mLPO) and liver deoxyribonucleic acid (DNA) fragmentation were assessed spectrophotometrically. Caspases 3 and 9 were determined by Enzyme-Linked Immunosorbent Assay (ELISA) technique. Cytochrome c, P53, Bcl-2-associated X protein (Bax), and B-cell lymphoma-2 (Bcl2) were determined via immunohistochemistry. Phytochemical constituents of the crude methanol extract of Globimetula braunii were determined via the Gas Chromatography-Mass Spectrometry (GC-MS) analysis., Results: There was large amplitude mPT induction by malaria parasites, extract and fractions of Globimetula braunii . At 400 mg/kg, HF significantly ( p  < 0.01) downregulated mATPase activity, and mLPO in both (susceptible and resistant) models, caused DNA fragmentation ( P  < 0.0001), induced caspases activation, P53, bax and cytochrome c release but downregulated Bcl2 in both models. The GC-MS analysis of methanol extract of Globimetula braunii showed that α-amyrin is the most abundant phytochemical., Conclusion: The n -hexane fraction of Globimetula braunii induced mitochondrial-mediated apoptosis through the opening of the mitochondrial pore, fragmentation of genomic DNA, increase in the levels of P53, bax, caspase 3 and 9 activation and cytochrome c release with concomitant decrease in the level of Bcl2. α-Amyrin is a triterpene with apoptotic effects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The antidiabetic properties of ferulic acid and its protective role against Fe 2+ -induced oxidative pancreatic injury were investigated in this study using in vitro and ex vivo models. Induction of oxidative injury in the pancreas was achieved by incubating normal pancreatic tissue with 0.1 mM FeSO 4 and treated by co-incubating with different concentrations of ferulic acid for 30 min at 37°C. Ferulic acid inhibited the activities of α-glucosidase, α-amylase, and pancreatic lipase significantly (p < .05) and promoted glucose uptake in isolated rat psoas muscles. Induction of oxidative pancreatic injury caused significant (p < .05) depletion of glutathione (GSH) level, superoxide dismutase (SOD), and catalase activities, as well as elevation of malondialdehyde (MDA) and nitric oxide (NO) levels, acetylcholinesterase and chymotrypsin activities. Treatment of tissues with ferulic acid significantly (p < .05) reversed these levels and activities. LC-MS analysis of the extracted metabolites revealed 25% depletion of the normal metabolites with concomitant generation of m-Chlorohippuric acid, triglyceride, fructose 1,6-bisphosphate, and ganglioside GM1 in oxidative-injured pancreatic tissues. Treatment with ferulic acid restored uridine diphosphate glucuronic acid and adenosine tetraphosphate and generated P1,P4-Bis(5'-uridyl) tetraphosphate and L-Homocysteic acid, while totally inactivating oxidative-generated metabolites. Ferulic acid also inactivated oxidative-activated pathways, with concomitant reactivation of nucleotide sugars metabolism, starch and sucrose metabolism, and rostenedione metabolism, estrone metabolism, androgen and estrogen metabolism, porphyrin metabolism, and purine metabolism pathways. Taken together, our results indicate the antidiabetic and protective potential of ferulic acid as depicted by its ability to facilitate muscle glucose uptake, inhibit carbohydrate and lipid hydrolyzing enzymes, and modulate oxidative-mediated dysregulated metabolisms. PRACTICAL APPLICATIONS: There have been increasing concerns on the side effects associated with the use of synthetic antidiabetic drug, coupled with their expenses particularly in developing countries. This has necessitated continuous search for alternative treatments especially from natural products having less or no side effects and are readily available. Ferulic acid is among the common phenolics commonly found in fruits and vegetables. In this present study, ferulic acid was able to attenuate oxidative stress, cholinergic dysfunction, and proteolysis in oxidative pancreatic injury, as well as inhibit carbohydrate digesting enzymes. Thus, indicating the ability of the phenolic to protect against complications linked to diabetes. Crops rich in ferulic acid maybe beneficial in managing this disease., (© 2021 Wiley Periodicals LLC.)

Pro-inflammatory signaling, cell death, and metalloproteinases activation are events in Plasmodium infection. However, it is not known if treatment with mefloquine (MF), and curcumin (CM) supplementation, will modulate these conditions. Malaria was induced in two different studies using susceptible (NK 65, study 1) and resistant (ANKA, study 2) strains of mouse malaria parasites (Plasmodium berghei) in thirty male Swiss mice (n = 5) in each study. Following confirmation of parasitemia, mice received 10 mL/kg distilled water (infected control), MF (10 mg/kg), MF and CM (25 mg/kg), MF and CM (50 mg/kg), CM (25 mg/kg) and CM (50 mg/kg). Five mice (not infected) were used as control. After treatment, the animals were sacrificed, serum obtained and liver mitochondria were isolated. Serum Tumour Necrosis Factor alpha (TNF-α), C-reactive protein (CRP), Interleukins-1 beta (IL-1β) and Interleukins-6 (IL-6) as well as caspases-3, 9 (C3 and C9), p53, serum troponin I (TI) and creatine kinase (CK), were assayed using ELISA techniques. Mitochondrial membrane permeability transition (mPT) pore opening, mitochondrial F 0 F 1 ATPase activity, and lipid peroxidation (mLPO) were determined spectrophotometrically. Matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) expressions were determined using electrophoresis. CM supplementation (25 mg/kg) significantly decreased serum p53, TNF-α, CRP and IL-6 compared with MF. In the resistant model, CM prevented mPT pore opening, significantly decreased F 0 F 1 ATPase activity and mLPO. MF activated caspase-3 while supplementation with CM significantly decreased this effect. Furthermore, MMP-2 and MMP-9 were selectively expressed in the susceptible model. Malarial treatment with mefloquine elicits different cell death responses while supplementation with curcumin decreased TI level and CK activities., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The leaves of Polydora serratuloides , with the synonym Vernonia perrottetii are widely used as purgative agents for gastrointestinal problems, and other members of Vernonieae have been used in African traditional medicine for decades. A new sesquiterpene lactone of the keto-hirsutinolide type, 13-acetoxy-1(4 β ),5(6) β -diepoxy-8 α -(senecioyloxy)-3-oxo-1,7(11)-germacradiene-12,6-olide 1 , was isolated from the hexane extract of its leaves, in addition to the known 13-acetoxy-1,4 β -epoxy-8 α -(senecioyloxy)-3-oxo-1,5,7(11)-germacratriene-12,6-olide 2 . Three common flavonoids (apigenin 3 , luteolin 4 and velutin 5 ) were also isolated. The antibacterial and quorum sensing inhibitory activities of compounds 1 and 2 and crudes extracts showed limited activity on Bacillus subtilis and Staphylococcus aureus , with no activity on Gram negative bacteria. However, quorum sensing (QSI) experiments indicated that 1 and 2 , and the four crude extracts had interesting inhibitory activity on the biosensor organism, Chromobacterium violaceum ATCC 12472 in the range of 0.33-5.25 mg mL -1 , with compound 1 being the most effective at 0.33 mg mL -1 .

Ethnopharmacological Relevance: 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., Aim: This study investigates the effect of Raffia palm wine on dysregulated lipid metabolic pathways in testicular tissues of type 2 diabetic (T2D) rats., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study investigated the therapeutic mechanism of Cola nitida seeds on diabetic cardiomyopathy in hearts of diabetic rats. Type 2 diabetic (T2D) rats were treated with C. nitida infusion at 150 or 300 mg/kg body weight (bw). The rats were sacrificed after 6 weeks of treatment, and their hearts harvested. There was an upsurge in oxidative stress on induction of T2D as depicted by the depleted levels of glutathione, superoxide dismutase and catalase activities, and elevated malondialdehyde level. The activities of acetylcholinesterase, and ATPase were significantly elevated, with suppressed ENTPDase and 5'nucleotodase activities in hearts of T2D rats depicting cholinergic and purinergic dysfunctions. Induction of T2D further led to elevated activity of ACE and altered myocardial morphology. Treatment with C. nitida infusion led to reversal of these biomarkers' activities and levels, while maintaining an intact morphology. The infusion caused decreased lipase activity and depletion of diabetes-generated cardiac lipid metabolites, while concomitantly generating saturated and unsaturated fatty acids, fatty esters and alcohols. There was also an inactivation of plasmalogen synthesis and mitochondrial beta-oxidation of long chain saturated fatty acids pathways in T2D rats treated with C. nitida infusion. These results indicate the therapeutic effect of C. nitida infusion against diabetic cardiomyopathy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The antidiabetic effect of l-leucine has been attributed to its modulatory effect on glucose uptake and lipid metabolism in muscles. However, there is a dearth on its effect on glucose metabolism in muscles. Thus, the present study investigated the effect of l-leucine - stimulated glucose uptake on glucose metabolism, dysregulated lipid metabolic pathways, redox and bioenergetic homeostasis, and proteolysis in isolated psoas muscle from Sprague Dawley male rats. Isolated psoas muscles were incubated with l-leucine (30-240 μg/mL) in the presence of 11.1 mMol glucose at 37 ˚C for 2 h. Muscles incubated in only glucose served as the control, while muscles not incubated in l-leucine and/or glucose served as the normal control. Metformin (6.04 mM) was used as the standard antidiabetic drug. Incubation with l-leucine caused a significant increase in muscle glucose uptake, with an elevation of glutathione levels, superoxide dismutase, catalase, E-NTPDase and 5'nucleotidase activities. It also led to the depletion of malondialdehyde and nitric oxide levels, ATPase, chymotrypsin, acetylcholinesterase, glycogen phosphorylase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and lipase activities. There was an alteration in lipid metabolites, with concomitant activation of glycerolipid metabolism, fatty acid metabolism, and fatty acid elongation in mitochondria in the glucose-incubated muscle (negative control). Incubation with l-leucine reversed these alterations, and concomitantly deactivated the pathways. These results indicate that l-leucine-enhanced muscle glucose uptake involves improved redox and bioenergetic homeostasis, with concomitant suppressed proteolytic, glycogenolytic and gluconeogenetic activities, while modulating glucose - lipid metabolic switch.

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 FeSO 4 . 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Erukainure, Chukwuma, Matsabisa, Javu, Salau, Koorbanally and Islam.)

The use of medicinal plants in the treatment of malaria is gaining global attention due to their efficacy and cost effectiveness. This study evaluated the bioactivity-guided antiplasmodial efficacy and immunomodulatory effects of solvent fractions of Diospyros mespiliformis in mice infected with a susceptible strain of Plasmodium berghei (NK 65). The crude methanol extract of the stem of D. mespiliformis (DM) was partitioned between n-hexane, dichloromethane, ethyl acetate and methanol. Male Swiss mice (20 ± 2 g) infected with P. berghei were grouped and treated with vehicle (10 mL/kg, control), Artemether lumefantrine (10 mg/kg), 100, 200 and 400 mg/kg of n-hexane, dichloromethane, ethyl acetate and methanol fractions of D. mespiliformis for seven days. Blood was obtained for heme and hemozoin contents while serum was obtained for inflammatory cytokines and immunoglobulins G and M assessments. Liver mitochondria were isolated for mitochondrial permeability transition (mPT), mitochondrial F 1 F 0 ATPase (mATPase) and lipid peroxidation (mLPO) assays. The GC-MS was used to identify the compounds present in the most potent fraction. The dichloromethane fraction had the highest parasite clearance and improved hematological indices relative to the drug control. The heme values increased, while the hemozoin content significantly (P < 0.05) decreased compared with the drug control. The highest dose of HF and MF opened the mPT pore while the reversal effects of DF on mPT, mATPase and mLPO were dose-dependent. The levels of IgG, IgM and TNFα in the DF group were significantly higher than the drug control, while the IL-1β and IL-6 values did not vary linearly with the dose. Lupeol and Stigmastan-3,5-diene were the most abundant phytochemicals in the DF. The outcome of this study showed that the DF has immunomodulatory effects in infected mice, reduced proliferation of the malaria parasite and thus protect liver cells.

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 FeSO 4 . 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 LD 50 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.

The present study investigates the cytotoxic effect of the chemical fractions of Allium cepa (yellow variety) on Human Embryonic Kidney (HEK293) cells. Allium cepa was blended into paste and macerated in distilled water before subjecting to liquid-liquid fractionation, yielding the dichloromethane, ethyl acetate (EtOAc), butanol, and aqueous fractions. Their cytotoxicity on HEK293 cells were evaluated via MTT assay. The cytotoxic fraction (EtOAc) was further evaluated for its oxidative, pro-inflammatory, and apoptotic effects on the cells. The incubation of cells with EtOAc led to depleted level of GSH, SOD, and catalase activities, and elevated levels of malondialdehyde, nitric oxide, and myeloperoxidase as well as apoptotic activities. GC-MS analysis of EtOAc revealed allyl ionone, pentadecanoic acid, and phytol acetate as the predominant fatty acids, while ergost-7-en-3β-ol, campesterol, cycloartenol-3β acetate, sitosterol, and fucosterol as the predominant sterols. These results portray the cytotoxic effect of the EtOAc fraction of A. cepa on HEK293 cells. PRACTICAL APPLICATIONS: There have been increasing concerns in the toxicity and safety of foods. Allium cepa (onions) is among the common globally grown and consumed plant food. This study investigated its cytotoxic effect on normal Human Embryonic Kidney (HEK293) Cells. Although only the ethyl acetate fraction was cytotoxic against the cell line, it, however, portrays a need for caution in its usage., (© 2020 Wiley Periodicals LLC.)

A library of pyrazole-thiazolidinone conjugates was synthesized using a molecular hybridization approach through a Vilsmeier-Haack reaction. The compounds were tested for anti-microbial activity against two Gram-positive bacteria (Staphylococcus aureus and methicillin-resistant Staphylococcus aureus) and four Gram-negative bacteria (Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia and Pseudomonas aeruginosa). Among the compounds tested, 3-((2,4-dichlorophenyl)-1-(2,4-dinitrophenyl)-1H-pyrazol-yl)methylene)hydrazinecarbothioamide (3a) and 2-((3-(2-chlorophenyl)-1-(2,4 dinitrophenyl)-1H-pyrazol-4-yl)methyleneamino)thiazolidin-4-one (4b) emerged as the most potent anti-microbial compounds with minimum bactericidal concentrations of < 0.2 µM against MRSA and S. aureus. Structure-activity relationship analysis further revealed that the presence of 2,4-dichloro moiety surprisingly influenced the activity of the compounds. Molecular docking studies of the compounds into the crystal structure of topoisomerase II and topoisomerase IV suggest that compounds 3a and 4b preferably interact with the targets through hydrogen bonding.

Background: The therapeutic effect of Cola nitida hot infusion against diabetes hepatic injury was investigated in livers of diabetic rats. Cola nitida was infused in boiling water and concentrated., Methods: The concentrated infusion was administered to T2D rats at low and high doses (150 and 300 mg/kg body weight (bw), respectively). The normal group (positive control) and another diabetic group (negative control) were administered distilled water, while metformin served as the standard drug. A toxic group that consists of normal rats administered a high dose of C. nitida. After 6 weeks, the rats were sacrificed, and their livers were collected. They were assayed for oxidative stress markers, myeloperoxidase, acetylcholinesterase and ATPase activities. Hepatic lipid metabolites were profiled with GC-MS and their metabolic pathways were analyzed using the MetaboAnalyst 4.0 online server., Results: Treatment with C. nitida caused a significant elevation of glutathione level and SOD activity, while concomitantly inhibiting lipid peroxidation, myeloperoxidase, acetylcholinesterase and ATPase activities in hepatic tissues of the rats. Treatment with C. nitida also caused significant depletion of diabetes-generated lipid metabolites, with concomitant generation of fatty esters and steroids as well as inactivation of diabetes-activated pathways., Conclusion: These data demonstrate the therapeutic effect of C. nitida against diabetic hepatotoxicity in diabetic rats., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The infusion of Chrysophyllum albidum was investigated for its antidiabetic mechanism by studying its ability to promote glucose uptake and utilization as well as its modulatory effect on metabolic activities linked to type 2 diabetes in isolated psoas muscle. Isolated psoas muscle was incubated with different concentrations of the infusion in the presence of glucose at 37°C for 2 hr. The infusion improved muscle glucose uptake, with concomitant elevated muscular levels of glutathione, superoxide dismutase, catalase, and ectonucleotidase activities, while depleting malondialdehyde, nitric oxide, adenosine triphosphatase, acetylcholinesterase, glycogen phosphorylase, glucose 6-phosphatase, fructose-1,6-biphosphatase, and lipase activities. It also maintained muscular morphology, while increasing magnesium, calcium, and iron levels. The infusion inhibited α-glucosidase and α-amylase activities in vitro. LC-MS analysis of the infusion revealed the presence of phenolics. These results indicate that C. albidum may mediate antidiabetic activities by stimulating muscle glucose uptake and modulation of key metabolisms linked to diabetes. PRACTICAL APPLICATIONS: The African star apple is among the underutilized fruits consumed for nutritional and medicinal purposes in Western Africa. The fruits are usually wasted during its season leading to postharvest loss owing to poor utilization. The present study gives credence to its use in treating diabetes and its complications. Thus, the fruits can be utilized in the development of cheap and affordable nutraceuticals for the management of diabetes which has been reported for its high-cost treatment. Utilization of the fruits will also reduce its postharvest loss and improve its economic values., (© 2020 Wiley Periodicals LLC.)

Objectives: This study was aimed at investigating neuroprotective effect of catechol on redox imbalance, cholinergic dysfunctions, nucleotide hydrolysing enzymes activities, and dysregulated metabolic pathways in iron-mediated oxidative brain injury., Methods: Oxidative injury was induced in brain tissues by incubating with 0.1 mm FeSO 4 and treated with different concentrations of catechol., Key Findings: Catechol significantly elevated glutathione level, superoxide dismutase and catalase activities, while depleting malondialdehyde and nitric oxide levels. It also inhibited the activities of acetylcholinesterase, butyrylcholinesterase, and ATPase, with concomitant elevation of ENTPDase activity. GC-MS analysis revealed that treatment with catechol completely depleted oxidative-generated lipid metabolites. While LC-MS analysis revealed depletion of oxidative-generated metabolites in brain tissues treated with catechol, with concomitant restoration of oxidative-depleted metabolites. Catechol also led to reactivation of oxidative-inactivated taurine and hypotaurine, purine, glutathione, glycerophospholipid, nicotinate and nicotinamide, fructose and mannose, pyrimidine metabolisms and pentose phosphate pathways. Catechol was predicted in silico to be permeable across the blood-brain barrier with a predicted oral LD 50 value of 100 mg/kg and a toxicity class of 3., Conclusion: These results suggest the neuroprotective effects of catechol in iron-mediated oxidative brain injury., (© 2020 Royal Pharmaceutical Society.)

Caseins are the most abundant milk proteins in mammalian species and are assembled in supra-macromolecular structures called micelles. In this study, the microstructural properties, particle size, and elemental composition of isolated casein from bovine milk and its therapeutic effect on oxidative and cholinergic activities linked to dementia in oxidative brain injury were investigated. SEM analysis of the isolated casein micelles from skimmed fresh bovine milk revealed spherical colloid aggregates, while TEM analysis revealed dispersed spherical particles with a mean size of 63.15 ± 4.77 nm. SEM-EDX analysis revealed clusters of carbon, oxygen, sulfur, copper, sodium, magnesium, potassium, iron, and selenium. Treatment of oxidative brain injury with the isolated casein micelles led to elevated levels of GSH, SOD, catalase, ENTPDase, 5'NTPase activities, while concomitantly suppressing MDA, cholesterol, HDL-c levels, acetylcholinesterase and lipase activities. Treatment with the isolated casein micelles led to complete depletion of oxidative generated lipid metabolites, while deactivating oxidative-activated lipid metabolic pathways. These results indicate the microstructural properties, particle size, elemental composition, and antioxidant neuroprotective effect of casein micelles from bovine milk. Thus, demonstrating the nutraceutical properties of milk in the management of oxidative induced cognitive impairment.

The comparative phytochemicals, antioxidative and antidiabetic activities of Camellia sinensis (black tea) and Aspalathus linearis (rooibos tea) were studied in vitro and ex vivo. Concentrated infusions of the teas showed significant free radical scavenging activities in vitro. They significantly increased the glutathione level, superoxide dismutase and catalase enzyme activities in oxidative hepatic injury, while concomitantly depleting malondialdehyde level. The teas significantly inhibited intestinal glucose absorption and α-amylase activities, and elevated muscle glucose uptake. LCMS phytochemical profiling revealed the presence of hydroxycaffeic acid, l-threonate, caffeine, vanillic acid, n-acetylvaline, and spinacetin 3-glucoside in C. sinensis . While quinolinic acid, coumestrol, phloroglucinol, 8-hydroxyquercetagetin, umbelliferone, and ajoene were identified in A. linearis . These results portray the antioxidant and antidiabetic potencies of both teas, with A. linearis showed better activity compared to C. sinensis . These teas may thus be used as functional foods in the management of diabetes and other oxidative stress related metabolic disorders., Competing Interests: Conflict of interestThe authors report no conflict of interest., (© Association of Food Scientists & Technologists (India) 2020.)

The present study investigated the effect of raffia palm (Raphia hookeri) wine (RPW) on hyperglycemia-mediated lipid metabolites and pathways, functional chemistry and ultrastructural morphology of cerebellums in type 2 diabetes (T2D). T2D was induced in male Sprague-Dawley rats by feeding with 10% fructose ad libitum for 2 weeks before injecting intraperitoneally with 40 mg/kg bodyweight (bw) streptozotocin. Following confirmation of hyperglycemia at blood glucose >200 mg/dL, diabetic rats were treated with RPW at 150 and 300 mg/kg bw respectively. Metformin served as the standard drug. Negative and normal controls consisted of untreated diabetic and non-diabetic rats, respectively. After 5 weeks of treatment, the rats were humanely sacrificed, and their cerebellum excised from the harvested brains. GC-MS analysis revealed significant alterations in cerebellar lipid metabolites depicted by changes in unsaturated and saturated fatty acids, fatty - esters, alcohols, and amides, glycols and steroids on induction of T2D. Pathway enrichment analysis of the lipid metabolites revealed inactivation of arachidonic metabolic pathway following T2D induction. Treatment with both doses of RPW restored most of the metabolites, while reactivating arachidonic acid metabolism (high dose only). Low dose of RPW led to the activation of retinol metabolism. Both doses of RPW maintained cerebellar functional chemistry as revealed by FTIR analysis. TEM analysis revealed swollen mitochondria, depleted numbers of synaptic vesicles, and shrunk synaptic clefts following induction of T2D. These ultrastructural morphologies were improved in RPW-treated rats. These results portray the therapeutic potential of raffia palm wine in the management of neurodegenerative complications in T2D., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The antioxidant, antidiabetic, and anti-obesogenic potentials of different extracts (dichloromethane, ethyl acetate, ethanol, and aqueous) of the red honeybush (Cyclopia genistoides) tea were investigated in vitro and ex vivo. All extracts exhibited significant scavenging and reducing power activities, with the aqueous and ethyl acetate extracts being the most potent. In vitro antidiabetic analysis revealed the extracts to be potent inhibitors of α-glucosidase and lipase activities. All extracts increased catalase and SOD activities, and glutathione level in oxidative pancreatic injury. GC-MS analysis revealed the presence of fatty acids, fatty acid ester, phytols, sterols, saccharide, ketones, and triterpenes. These results imply that the sequential extracts of honeybush tea (particularly the aqueous and ethyl acetate extracts) may not only exhibit antioxidant potentials but also mediate anti-hyperglycemia activities by inhibiting lipid and carbohydrate digestion. PRACTICAL APPLICATIONS: Red honeybush tea is enjoyed widely in South Africa and around the world due to its no caffeine and very low tannin content, as well as many healthcare attributes. There are however no scientific reports for its sequential extraction of different solvents on antidiabetic effects. The different extracts of honeybush tea (particularly the aqueous and ethyl acetate extracts) inhibited lipid and carbohydrate digestive enzymes linked to type 2 diabetes (T2D), as well as modulate oxidative pancreatic injury. These findings will promote its utilization as a potential nutraceutical in the management of diabetes and its complications., (© 2020 Wiley Periodicals LLC.)

The protective effect of caffeic acid on ferric-induced pancreatic injury was investigated using ex vivo and in silico models. Incubation of pancreatic tissues with Fe 2+ led to significant depleted levels of glutathione (GSH) and SOD and catalase activities, with concomitant elevated levels of malondialdehyde (MDA) and nitric oxide (NO) and acetylcholinesterase and α-chymotrypsin activities. Treatment with caffeic acid led to significant reversion of these levels and activities. Molecular docking revealed a higher binding affinity of caffeic acid with acetylcholinesterase via hydrogen bonding, Pi-Pi stacking, and Van der Waals interactions. FTIR spectroscopy of pancreatic metabolite revealed little or no effect by caffeic acid on functional groups in ferric-induced injured pancreas. The LC-MS analysis of the metabolites revealed Fe 2+ caused a 20% depletion of the normal metabolites, with concomitant generation of glyceraldehyde and 3,4-dihydroxymandelaldehyde. Treatment with caffeic acid led to the restoration of TG(22:4(7Z,10Z,13Z,16Z)/24:0/22:5(7Z,10Z,13Z,16Z,19Z)) and dTDP-D-glucose, while depleting glyceraldehyde as well as activating gluconeogenesis. These results indicate the ability of caffeic acid to protect against ferric toxicity by exacerbating antioxidative activities, with concomitant inhibition of MDA and NO levels while deactivating metabolic pathways linked to oxidative stress.

The therapeutic effect of phenolics on neurodegenerative diseases has been attributed to their potent antioxidant properties. In the present study, the neuroprotective activities of vanillin and vanillic acid were investigated in Fe 2+ - induced oxidative toxicity in brain tissues by investigating their therapeutic effects on oxidative imbalance, cholinergic and nucleotide-hydrolyzing enzymes activities, dysregulated metabolic pathways. Their cytotoxicity was investigated in hippocampal neuronal cell lines (HT22). The reduced glutathione level, SOD and catalase activities were ameliorated in tissues treated with the phenolics, with concomitant depletion of malondialdehyde and nitric oxide levels. They inhibited acetylcholinesterase and butyrylcholinesterase activities, while concomitantly elevated ATPase activity. Treatment with vanillin led to restoration of oxidative-depleted metabolites and reactivation of the pentose phosphate and purine metabolism pathways, with concomitant activation of pathways for histidine and selenoamino metabolisms. While vanillic acid restored and reactivated oxidative-depleted metabolites and pathways but did not activate any additional pathway. Both phenolics portrayed good binding affinity for catalase, with vanillic acid having the higher binding energy of -7.0 kcal/mol. Both phenolics were not cytotoxic on HT22 cells, and their toxicity class were predicted to be 4. Only vanillin was predicted to be permeable across the blood brain barrier (BBB). These results insinuate that vanillin and vanillic acid confer a neuroprotective effect on oxidative brain damage, when vanillin being the most potent.

The neuroprotective activities of phenolics have been demonstrated in several studies, with their antioxidant properties playing an influential role. In this study, the therapeutic effect of ferulic acid was investigated on oxidative stress, purinergic and cholinergic enzymatic activities, and dysregulated metabolic pathways in oxidative brain injury. Ferulic acid significantly elevated the reduced glutathione (GSH) level, superoxide dismutase and catalase activities, and concomitantly depleted malondialdehyde and nitric oxide level. It also inhibited the activities of acetylcholinesterase and butyrylcholinesterase, and increased the activities of ATPase. LC-MS analysis of the metabolites revealed restoration of most depleted metabolites, with concomitant generation of dihydroferulic acid 4-O-glucuronide, diadenosine heptaphosphate, cis-4-decenoic acid, ganglioside GT3 (d18:0/23:0), phosphatidylinositol-3,4,5-trisphosphate, and phosphoribosyl-ATP on treatment with ferulic acid. Pathway analysis of the identified metabolites revealed reactivation of oxidative-inactivated pathways, with concomitant activation of histidine and inositol phosphate metabolic pathways. There was no cytotoxicity on incubation of ferulic acid with HT22 cells. Molecular docking studies revealed a high affinity for acetylcholinesterase, with a binding energy of - 7.4 kcal/mol. In silico simulation analysis predicted permeability of ferulic acid across blood brain barrier (BBB) and an oral LD 50 calculated value of 1772 mg/kg, with a toxicity class of 4. These results indicate the antioxidative and protective effects of ferulic acid in oxidative brain injury.

Ethnopharmacological Relevance: Buddleja saligna Willd (Loganiaceae), mostly indigenous to South Africa is traditionally used in the treatment cardio-dysfunctional related ailments amongst other diseases., Aims: The cardio-protective effect of B. saligna was investigated in ferric-induced oxidative cardiopathy., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Medicinal plants have long been recognized for their roles in the treatment and management of diabetes and its complications. The antioxidative and antidiabetic properties of Clerodendrum volubile flowers were investigated in vitro and ex vivo., Methods: The flowers were sequentially extracted with solvents of increasing polarity (n-hexane, ethyl acetate, ethanol and water). The concentrated extracts were subjected to in vitro antioxidant assays using the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Ferric reducing antioxidant power (FRAP) protocols. Their inhibitory activities were investigated on α-glucosidase, pancreatic lipases, pancreatic ATPase and glucose-6-phosphatase activities. Their anti-oxidative and anti-apoptotic effects on Fe 2+ -induced oxidative injuries were also investigated in pancreatic and hepatic tissues ex vivo., Results: The extracts showed potent free radical scavenging activity and significantly ( p  < 0.05) inhibited all studied enzymes. The GSH level was significantly ( p  < 0.05) elevated in both tissues with concomitant increase in superoxide dismutase (SOD) and catalase activities as well as reduced levels of malondialdehyde (MDA). The extracts significantly ( p  < 0.05) suppressed DNA fragmentation in hepatic tissue. These activities were dose-dependent. The ethanol extract showed the best activity and can be attributed to the synergetic effect of its chemical constituents identified via gas chromatography-mass spectroscopy (GC-MS)., Conclusion: These results suggest the antioxidative, antidiabetic and anti-obesogenic potentials of C. volubile flowers., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© Springer Nature Switzerland AG 2019.)

Crassocephalum rubens falls under the wild edible, under-cultivated traditional leafy vegetables (TLV) in Africa; it is used by locals in managing diabetes mellitus among other diseases. This study investigated the in vitro, ex vivo antioxidant and antidiabetic potentials of different extracts of C. rubens. The ameliorative effects of the extracts on Fe 2+ -induced oxidative injury was investigated ex vivo together with the effects of the aqueous extract on intestinal glucose absorption and muscle glucose uptake in freshly harvested tissues from normal rats. The aqueous extract was subjected to Liquid Chromatography-Mass Spectrometry (LC-MS) analysis to identify possible bioactive compounds which were then docked with the tested enzymes through in silico modeling. The extracts exhibited antioxidant activity, inhibited α-glucosidase and lipase enzyme activities, intestinal glucose absorption and enhanced muscle glucose uptake compared to controls. Sanguisorbic acid dilactone identified through LC-MS analysis showed a high binding affinity for catalase and lipase enzymes. PRACTICAL APPLICATIONS: The results of this study suggest that the aqueous extract of C. rubens possesses better antioxidant and possible antidiabetic potentials compared to other extracts which could be associated to the synergistic action of its identified bioactive compounds., (© 2019 Wiley Periodicals, Inc.)

Ethnopharmacological Relevance: 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., Aim: The antidiabetic effect of RPW and its possible mechanism of actions were investigated in diabetic rats., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Brain glucose uptake is usually reduced in type 2 diabetes owing to downregulation of brain glucose transporters. The ability of Vernonia amygdalina to stimulate glucose uptake as well as ameliorate glucose-induced oxidative stress and proinflammation were investigated in rat brain. Hot infusion of V. amygdalina leaves was incubated with rat brain tissues for 2 h in the presence of glucose. Another incubation with glucose only, served as negative control while metformin served as positive control. Incubation of brain tissues with V. amygdalina led to significant (p < 0.05) increase in glucose uptake, reduced glutathione, nitric oxide and non-thiol proteins levels, superoxide dismutase, catalase and ATPase activities, while concomitantly decrease in myeloperoxidase activity and malondialdehyde level compared to the negative control. Incubation with glucose only, led to the development of nitrate, amide II and amide I functional groups which were removed on incubation with the infusion. LC-MS analysis revealed depletion of oxidative stress-induced 2-keto-glutaramic acid and cysteinyl-tyrosine metabolites in brain tissues, with concomitant generation of S-formylglutathione and adenosine tetraphosphate by the infusion. Pathway analysis of the metabolites revealed an activation of pyruvate metabolism pathway in the negative control, with the infusion reducing the intensity fold. LC-MS analysis of the infusion revealed the presence of l-serine, l-cysteine, l-proline, nicotinic acid, cumidine, salicylic acid, isoquinoline, 3-methyl-, and γ-octalactone. Except for l-serine, l-cysteine and l-proline, the other compounds were predicted to be permeable across the blood brain barrier. These results indicate the brain glucose uptake stimulatory and neuroprotective effect of V. amygdalina.

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., (© 2018 Wiley Periodicals, Inc.)

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 Fe 2+ -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 Fe 2+ -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., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

In this study, we identified bioactive compounds from the ethanolic extracts of the leaves, stem bark and root bark of Acalypha wilkesiana through GC-MS analysis and investigated the effects of these extracts on some of the enzymes linked to type 2 diabetes. Plant parts were extracted sequentially with ethyl acetate, ethanol and water. GC-MS analysis revealed the presence of long-chain alkyl acids, esters, ketones and alcohols including phytol and phytol acetate along with some secondary metabolites such as xanthone, vitamin E and various types of sterols including stigmasterol, campesterol and sitosterol. Ethanolic extracts of all the parts showed a dose- -dependent inhibition of α-glucosidase and α-amylase activity. The extracts also demonstrated anti-lipase activity. The ethanolic extract of root bark showed the highest inhibition of enzymes compared to other extracts. The EC50 values (concentrations for 50 % inhibition) of α-glucosidase, α-amylase and lipase inhibition were 35.75 ± 1.95, 6.25 ± 1.05 and 101.33 ± 5.21 μg mL-1, resp. The study suggests that A. wilkesiana ethanolic extracts have the ability to inhibit the activity of enzymes linked to type 2 diabetes. Further studies are needed to confirm the responsible bioactive compounds in this regard.

Chronic hyperglycemia has been implicated in the development of oxidative stress and as a major factor in etiology of secondary complication in diabetes. In the present study, the antidiabetic potential of Phragamenthra incana (P. incana) hot infusion and its possible inhibitory effects on carbohydrate digesting enzymes, promotion of muscle glucose uptake, and the antioxidative potentials in Fe 2+ -induced oxidative stress in hepatic tissue were investigated. The infusion significantly (p < 0.05) scavenged free radicals (DPPH) and displayed favourable ferric reducing antioxidant power (FRAP) with increasing concentrations. It also significantly ameliorated Fe 2+ -induced oxidative stress in hepatic tissues by increasing superoxide dismutase (SOD) and catalase activities and depleting malondialdehyde (MDA) level. The results further showed that the infusion significantly (p < 0.05) inhibited α-amylase and α-glucosidase activity, and enhanced muscle glucose uptake, with and without insulin. Liquid Chromatography-Mass Spectroscopy (LCMS) analysis of the infusion revealed the presence of 2-methoxythiazole; l-cysteine; nicotinic acid; S-methyl-l-cysteine; isoquinoline, 1-methyl-; and 1H-indole-2,3-dione,5-methyl. The results of this study suggest that the observed antidiabetic and antioxidative potentials of P. incana could be attributed to its identified phytochemical constituents, however, this supports folkloric medicinal use of this plant., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Linkers play major roles in conjugation chemistry toward the advancement of drug discovery. Two different series of fluorinated linkers were introduced to the backbone of a model peptide using solid phase peptide synthesis. These fluorinated linkers have the potential to conjugate two asymmetrical groups. This has not been done using other fluorinated linkers. This study deals with application of linkers with S, N, and O terminals and reports on the investigation of their chemoselectivity and activity for branching peptide backbones using a chosen model peptide. These fluorinated linkers have unique properties that will make it possible for a large diversity of bioconjugated chemicals for different bioapplications to be designed and synthesized.

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., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Considerable attention has been devoted to fluorinated compounds due to their unique and interesting properties. Many modern pharmaceuticals contain fluorinated substituents, which are commonly synthesized using selective fluorinating reagents. Decafluorobiphenyl (DFBP) as a fluorinated linker is susceptible to nucleophilic attack. This nucleophilic reaction has been widely studied using various nucleophiles. Sulfur and nitrogen containing nucleophiles have been of particular interest, especially in bioconjugated reactions. This review focuses on the S N Ar reactivity of DFBP in formation of C-X (X = S, N) bonds, to be applied in bioconjugation in organic chemistry. The review aims to highlight the crucial factors that govern the chemistry behind the activation of F-C Ar -C Ar -F bonds as a linker in the synthesis of novel peptides, proteins, and biologics.

The present study aimed to investigate the effects of the various parts of Ficus carica L. (figs) on antioxidant, antidiabetic, and antiobesogenic effects in vitro. Fruit, leaves, and stembark of the F. carica plant were sequentially extracted using organic and inorganic solvents and their total polyphenol and flavonoid contents were estimated. The effects of the extracts on antioxidative, antidiabetic (inhibition of α-amylase and α-glucosidase enzymes), and antiobesogenic (antilipase) activities were measured using several experimental models. The fruit ethanolic extract contained a high quantity of polyphenols and flavonoids (104.67±5.51 μg/mL and 81.67±4.00 μg/mL) compared with all other extracts. The activity of the ethanolic extract of F. carica fruit was significantly (p<0.05) higher than all other extracts and parts of the plant in terms of antioxidative, antidiabetic, and antiobesogenic effects. The IC 50 values of the fruit ethanolic extract in terms of antioxidative (134.44±18.43 μg/mL), and inhibition of α-glucosidase (255.57±36.46 μg/mL), α-amylase (315.89±3.83 μg/mL), and pancreatic lipase (230.475±9.65 μg/mL) activity indicate that the activity of fruit ethanolic extract is better than all other extracts of the plant. The gas chromatography-mass spectroscopy analysis of the fruit ethanolic extract showed the presence of a number of bioactive compounds such as butyl butyrate, 5-hydroxymethyl furfural, 1-butoxy-1-isobutoxy butane, malic acid, tetradecanoic acid, phytol acetate, trans phytol, n-hexadecanoic acid, 9Z,12Z-octadecadienoic acid, stearic acid, sitosterol, 3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one, and 2,4,5-trimethyl-2,4-dihydro-3H-pyrazol-3-one. The results of this study suggest that the ethanolic extract of the fruit of F. carica may have potential antidiabetic and antiobesogenic agents., (Copyright © 2017. Published by Elsevier B.V.)