scholarly journals Discovery Potent of Thiazolidinedione Derivatives as Antioxidant, α-Amylase Inhibitor, and Antidiabetic Agent

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 24
Author(s):  
Manal Y. Sameeh ◽  
Manal M. Khowdiary ◽  
Hisham S. Nassar ◽  
Mahmoud M. Abdelall ◽  
Suliman A. Alderhami ◽  
...  
Keyword(s):  
Chemical Reactivity ◽  
Day Treatment ◽  
Radical Scavenging ◽  
Treatment Protocol ◽  
Docking Simulation ◽  
Diabetic Rat ◽  
Reference Drug ◽  
Ppar Γ

This work aimed to synthesize safe antihyperglycemic derivatives bearing thiazolidinedione fragment based on spectral data. The DFT theory discussed the frontier molecular orbitals (FMOs), chemical reactivity of compounds, and molecular electrostatic potential (MEP) to explain interaction between thiazolidinediones and the biological receptor. α-amylase is known as the initiator-hydrolysis of the of polysaccharides; therefore, developing α-amylase inhibitors can open the way for a potential diabetes mellitus drug. The molecular docking simulation was performed into the active site of PPAR-γ and α-amylase. We evaluated in vitro α-amylase’s potency and radical scavenging ability. The compound 6 has the highest potency against α-amylase and radical scavenging compared to the reference drug and other members. They have been applied against anti-diabetic and anti-hyperlipidemic activity (in vivo) based on an alloxan-induced diabetic rat model during a 30-day treatment protocol. The most potent anti hyperglycemic members are 6 and 11 with reduction percentage of blood glucose level by 69.55% and 66.95%, respectively; compared with the normal control. Other members exhibited moderate to low anti-diabetic potency. All compounds showed a normal value against the tested biochemical parameters (CH, LDL, and HDL). The ADMET profile showed good oral bioavailability without any observed carcinogenesis effect.

scholarly journals Antioxidant and Hypolipidemic Effects of Methanolic Root Extract of Chromolaena odorata in Alloxan-induced Diabetic Rats

2020 ◽  
Vol 14 (2) ◽  
pp. 63-70
Author(s):  
Oluyemisi Omotayo Omonije ◽  
◽  
Abubakar Ndaman Saidu ◽  
Hadiza Lami Muhammad ◽  
◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Density Lipoprotein ◽  
Reducing Power ◽  
Diabetic Rat ◽  
Albino Rats ◽  
Root Extract ◽  
Chromolaena Odorata

Background: Chromolaena odorata (C. odorata) is a medicinal plant with hypoglycemic effect known in traditional medicine. The present study investigated the in vitro antioxidant and in vivo anti-hyperglycemic effect of the methanol root extract of C. odorata in rats. Methods: Phytochemical compositions were evaluated, using standard procedures while the antioxidant activities were examined, using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and ferric reducing power (FRAP) assays. Twenty albino rats were administered 120 mg/kg of body weight (bw) alloxan and were divided into four groups of five animals each. Groups A to D were treated with 2 ml/kg of normal saline, 300 mg/kg, 500 mg/kg bw extract and 5 mg/kg bw glibenclamide, respectively, through oral route for 14 days. Blood samples were collected and prepared for the analysis of serum lipids profile. Results: The extract contained tannins (54.76±4.08 mg/100 g), saponins (322.78±17.35 mg/100 g), glycosides, alkaloids (74.34±6.08 mg/100 g), flavonoids (79.63±4.55 mg/100 g), phenols (154.32±11.21 mg/100 g), glycosides, steroids and reducing sugar. The extract promoted the inhibition of DPPH radicals with IC50 values of 191.68±1.68 µg/mL. In comparison with the untreated controls, total cholesterol, Low Density Lipoprotein (LDL)-cholesterol and triglycerides were significantly reduced (P<0.05) following treatment with C. odorata extract while high density lipoprotein (HDL)-cholesterol, was significantly increased. Conclusion: The C. odorata extract exhibited antioxidant and hypolipidemic effects in alloxan-induced diabetic rat, thus could be considered as a natural product in the management of dyslipidemia secondary to diabetes.

scholarly journals IN VITRO ANTIOXIDANT POTENTIALS AND HEPATOPROTECTIVE EFFECTS OF Asystasia vogeliana (BENTH) LEAF EXTRACTS AGAINST PARACETAMOL-INDUCED HEPATIC INJURY IN RATS

2020 ◽  
Vol 8 (6) ◽  
pp. 839-848
Author(s):  
Emeka Hillary Ugwuanyi ◽  
◽  
Chukwuneke Udem Samuel ◽  
Ifeanyi Innocent Madubuinyi ◽  
◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Radical Scavenging ◽  
In Vitro Assays ◽  
Distilled Water ◽  
Leaf Extracts ◽  
Group V ◽  
Reference Drug ◽  
Group I

This study was aimed to investigate the antioxidant potentials of methanol and petroleum ether leaf extracts of Asystasia vogeliana against paracetamol-induced liver injury in rats. For estimation of antioxidant potentials, in vitro radical scavenging assays were carried out using DPPH, FRAP, and ABTS. For in vivo study, twenty-five male Wistar rats weighing 100-120 g were randomized and assigned into 5 groups (I-V, n=5). Further, Paracetamol (PCM) at 2 g/kg was used to induce acute hepatotoxicity orally. Rats in group I received distilled water (10 ml/kg) only. While, the rats of groups II, III, and IV received MLEAV (200 mg/kg), PLEAV (200 mg/kg), and a standard hepatoprotective reference drug silymarin (25 mg/kg) respectively for 5 days before PCM induction. Rats in group V received distilled water for 5 days before PCM induction. Blood and liver samples were collected for hematology, serum biochemistry, and histopathology analyses using standard procedures. In vitro assays revealed that MLEAV showed significant (P < 0.05) increases in antioxidant activity compared with PLEAV. Further, significant (P < 0.05) reductions in the activities of ALT and ALP while a significant (P < 0.05) increases in the activity of antioxidant enzymes (CAT, SOD, and GPx) were reported in the group II and III compared with group V. There were also no observable lesions in their hepatocytes. Results of the study can be concluded that MLEAV elicited more in vitro and in vivo antioxidant activities than PLEAV, thus it protects the liver of rat from PCM-induced hepatotoxicity. Therefore, MLEAV could be used as a hepatoprotective agent for the clinical management of liver damage.

Hepato- and Nephroprotective Effects of the Polyphenol Concentrate From Cabernet Sauvignon Grape Varieties Cultivated in Kazakhstan in the Experimental Model Of CCL4-Induced Toxicity

2017 ◽  
Vol 9 (03) ◽  
Author(s):  
Nurgozhin T. ◽  
Sergazy S. H. ◽  
Adilgozhina G. ◽  
Gulyayev A. ◽  
Shulgau Z. ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Experimental Model ◽  
Lethal Dose ◽  
Radical Scavenging ◽  
Cabernet Sauvignon ◽  
Intragastric Administration ◽  
Liver And Kidney ◽  
Antioxidant Stress

Objective:This study investigates the hepatoprotective effect and the antioxidant role of polyphenol concentrate in the experimental model of carbon tetrachloride (CCl4) induced toxicity. Methods: Antioxidant activity of Cabernet Sauvignon grape polyphenol were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), 2,2’-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.+). In addition, the effects of polyphenol concentrate on the survival of Wistar rats in the toxicity model, was also investigated. The polyphenol concentrate was administered for 5 five days prior to injection of carbon tetrachloride in a sub-lethal dose of 300 mg/kg of animal body weight in order to perform histological examinations of the liver and kidney, and detect the levels of AST, ALT and bilirubin. Results: Administration of polyphenol concentrate increased animal survival in the experimental model. Moreover, the intragastric administration of polyphenol concentrate prior to the initiation of the experimental model of toxicity, which was caused by a sub-lethal CCl4 dose, reduced morphological injuries in the liver and kidney, decreased the AST and ALT levels of the blood serum. Discussion and conclusion: Our data demonstrate that polyphenol concentrate possesses an antioxidant potential both in vitro and in vivo by reducing antioxidant stress that was caused by CCl4 administration into rats.

Neurotrophic Properties of Silexan, an Essential Oil from the Flowers of Lavender-Preclinical Evidence for Antidepressant-Like Properties

2020 ◽  
Vol 54 (01) ◽  
pp. 37-46
Author(s):  
Kristina Friedland ◽  
Giacomo Silani ◽  
Anita Schuwald ◽  
Carola Stockburger ◽  
Egon Koch ◽  
...  
Keyword(s):  
Essential Oil ◽  
Hippocampal Neurons ◽  
Day Treatment ◽  
Neuronal Cell ◽  
Antidepressant Activity ◽  
In Vivo Models ◽  
Antidepressant Effects ◽  
Primary Hippocampal Neurons

Abstract Background Silexan, a special essential oil from flowering tops of lavandula angustifolia, is used to treat subsyndromal anxiety disorders. In a recent clinical trial, Silexan also showed antidepressant effects in patients suffering from mixed anxiety-depression (ICD-10 F41.2). Since preclinical data explaining antidepressant properties of Silexan are missing, we decided to investigate if Silexan also shows antidepressant-like effects in vitro as well as in vivo models. Methods We used the forced swimming test (FST) in rats as a simple behavioral test indicative of antidepressant activity in vivo. As environmental events and other risk factors contribute to depression through converging molecular and cellular mechanisms that disrupt neuronal function and morphology—resulting in dysfunction of the circuitry that is essential for mood regulation and cognitive function—we investigated the neurotrophic properties of Silexan in neuronal cell lines and primary hippocampal neurons. Results The antidepressant activity of Silexan (30 mg/kg BW) in the FST was comparable to the tricyclic antidepressant imipramine (20 mg/kg BW) after 9-day treatment. Silexan triggered neurite outgrowth and synaptogenesis in 2 different neuronal cell models and led to a significant increase in synaptogenesis in primary hippocampal neurons. Silexan led to a significant phosphorylation of protein kinase A and subsequent CREB phosphorylation. Conclusion Taken together, Silexan demonstrates antidepressant-like effects in cellular as well as animal models for antidepressant activity. Therefore, our data provides preclinical evidence for the clinical antidepressant effects of Silexan in patients with mixed depression and anxiety.

scholarly journals Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1343
Author(s):  
Balaji Venkataraman ◽  
Saeeda Almarzooqi ◽  
Vishnu Raj ◽  
Abdullah T. Alhassani ◽  
Ahmad S. Alhassani ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Activity Index ◽  
Nigella Sativa ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Ppar Γ ◽  
Anti Inflammatory ◽  
Ht 29

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders with increasing incidence and prevalence worldwide. Here, we investigated thymoquinone (TQ), a naturally occurring phytochemical present in Nigella sativa, for anti-inflammatory effects in colonic inflammation. To address this, we used in vivo (mice) and in vitro (HT-29 cells) models in this investigation. Our results showed that TQ treatment significantly reduced the disease activity index (DAI), myeloperoxidase (MPO) activity, and protected colon microscopic architecture. In addition, TQ also reduced the expression of proinflammatory cytokines and mediators at both the mRNA and protein levels. Further, TQ decreased phosphorylation of the activated mitogen-activated protein kinase (MAPK) signaling pathway and nuclear factor kappa B (NF-κB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. TQ significantly decreased proinflammatory chemokines (CXCL-1 and IL-8), and mediator (COX-2) mRNA expression in HT-29 cells treated with TNF-α. TQ also increased HT-29 PPAR-γ mRNA, PPAR-γ protein expression, and PPAR-γ promoter activity. These results indicate that TQ inhibits MAPK and NF-κB signaling pathways and transcriptionally regulates PPAR-γ expression to induce potent anti-inflammatory activity in vivo and in vitro models of colon inflammation.

scholarly journals Hepatoprotective studies on methanolic extract fractions of Lindernia ciliata and development of qualitative analytical profile for the bioactive extract

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Praneetha Pallerla ◽  
Narsimha Reddy Yellu ◽  
Ravi Kumar Bobbala
Keyword(s):  
Methanolic Extract ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Liver Homogenate ◽  
Reducing Power ◽  
Hepatoprotective Activity ◽  
Total Phenolic ◽  
Effective Fraction

Abstract Background The objective of the study is to evaluate the hepatoprotective activity of methanolic extract fractions of Lindernia ciliata (LC) and development of qualitative analytical profile of the bioactive fraction using HPLC fingerprinting analysis. All the fractions of methanolic extract of Lindernia ciliata (LCME) are assessed for their total phenolic, flavonoid contents and in vitro antioxidant properties by using DPPH, superoxide, nitric oxide, hydroxyl radical scavenging activities and reducing power assay. Acute toxicity study was conducted for all the fractions and the two test doses 50 and 100 mg/kg were selected for the hepatoprotective study. Liver damage was induced in different groups of rats by administering 3 g/kg.b.w.p.o. paracetamol and the effect of fractions were tested for hepatoprotective potential by evaluating serum biochemical parameters and histology of liver of rats. The effective fraction was evaluated for its antihepatotoxic activity against D-Galactosamine (400 mg/kg b.w. i.p.) and in vivo antioxidant parameters viz., Glutathione (GSH), Melondialdehyde (MDA) and Catalase (CAT) levels are estimated using liver homogenate. Results Among all the fractions, butanone fraction of LCME, (BNF-LCME) has shown better hepatoprotective activity and hence it is selected to evaluate the antihepatotoxicity against D-GaIN. The activity of BNF-LCME is well supported in in vitro and in vivo antioxidant studies and may be attributed to flavonoidal, phenolic compounds present in the fraction. Hence, BNF-LCME was subjected to the development of qualitative analytical profile using HPLC finger printing analysis. Conclusions All the fractions of LCME exhibited significant hepatoprotective activity and BNF-LCME (50 mg/kg) was identified as the most effective fraction.

scholarly journals Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4587
Author(s):  
Fanny d’Orlyé ◽  
Laura Trapiella-Alfonso ◽  
Camille Lescot ◽  
Marie Pinvidic ◽  
Bich-Thuy Doan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Biomedical Applications ◽  
Chemical Reactivity ◽  
Physical Stability ◽  
Chemical Properties ◽  
Building Blocks ◽  
Imaging Probes ◽  
Therapeutic Molecules

There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.

scholarly journals In Vitro and In Vivo Antioxidant Properties of Taraxacum officinale in Nω-Nitro-l-Arginine Methyl Ester (L-NAME)-Induced Hypertensive Rats

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 309
Author(s):  
Olukayode O. Aremu ◽  
Adebola O. Oyedeji ◽  
Opeoluwa O. Oyedeji ◽  
Benedicta N. Nkeh-Chungag ◽  
Constance R. Sewani Rusike
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Methyl Ester ◽  
Leaf Extract ◽  
Radical Scavenging ◽  
Free Radical Scavenging ◽  
Hypertensive Rats ◽  
Total Antioxidant

Oxidative stress has gained attention as one of the fundamental mechanisms responsible for the development of hypertension. The present study investigated in vitro and in vivo antioxidant effects of 70% ethanol-water (v/v) leaf and root extracts of T. officinale (TOL and TOR, respectively). Total phenolic and flavonoid content of plant extracts were assessed using Folin Ciocalteau and aluminium chloride colorimetric methods; while, 2,2-diphenyl-1-picrlhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) protocols were used to determine the free radical scavenging and total antioxidant capacities (TAC), respectively. The in vivo total antioxidant capacity and malondialdehyde acid (MDA) levels for lipid peroxidation tests were performed on organ homogenate samples from Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats treated with leaf extract, TOL (500 mg/kg/day) and TOR (500 mg/kg/day) for 21 days. Results showed that compared to TOR, TOL possessed significantly higher (p < 0.01) polyphenol (4.35 ± 0.15 compared to 1.14 ± 0.01) and flavonoid (23.17 ± 0.14 compared to 3 ± 0.05) content; free radical scavenging activity (EC50 0.37 compared to 1.34 mg/mL) and total antioxidant capacities (82.56% compared to 61.54% ABTS, and 156 ± 5.28 compared to 40 ± 0.31 FRAP) and both extracts showed no toxicity (LD50 > 5000 mg/kg). TOL and TOR significantly (p < 0.01) elevated TAC and reduced MDA levels in targets organs. In conclusion, T. officinale leaf extract possesses significant anti-oxidant effects which conferred significant in vivo antioxidant protection against free radical-mediated oxidative stress in L-NAME-induced hypertensive rats.

Aqueous extracts of avocado pear (Persea americana Mill.) leaves and seeds exhibit anti-cholinesterases and antioxidant activities in vitro

2016 ◽  
Vol 27 (2) ◽  
Author(s):  
Ganiyu Oboh ◽  
Veronica O. Odubanjo ◽  
Fatai Bello ◽  
Ayokunle O. Ademosun ◽  
Sunday I. Oyeleye ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Inhibitory Effect ◽  
Seed Extract ◽  
Persea Americana ◽  
Dependent Manner ◽  
Natural Treatment

AbstractAvocado pear (The inhibitory effects of extracts on AChE and BChE activities and antioxidant potentials (inhibition of FeThe extracts inhibited AChE and BChE activities and prooxidant-induced TBARS production in a dose-dependent manner, with the seed extract having the highest inhibitory effect and the leaf extract exhibiting higher phenolic content and radical scavenging abilities, but lower Fe chelation ability compared with that of the seed. The phytochemical screening revealed the presence of saponins, alkaloids, and terpenoids in both extracts, whereas the total alkaloid profile was higher in the seed extract than in the leaf extract, as revealed by GC-FID.The anti-cholinesterase and antioxidant activities of avocado leaf and seed could be linked to their phytoconstituents and might be the possible mechanisms underlying their use as a cheap and natural treatment/management of AD. However, these extracts should be further investigated in vivo.

Targeted chemical nucleases have a wide range of untapped applications in biological fields, including gene therapy

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Metal Complex ◽  
Dna Cleavage ◽  
Therapeutic Potential ◽  
Chemical Reactivity ◽  
Major Groove ◽  
Sequence Recognition ◽  
Wide Range ◽  
Chemical Nucleases

A feasible alternative to state-of-the-art enzymatic nucleases was created by regulating the cleavage activity of metal complexes using (covalent or non-covalent) homing agents. Targeted AMNs, unlike enzymatic nucleases, break DNA by an oxidative mechanism and can therefore permanently knock off genes. Compared to larger enzymatic nucleases, the modest size of the metal complex may aid cellular transfection. Furthermore, the painstaking construction of the sequence-specific probe permits a metal complex to be directed to dsDNA's minor or major groove. To direct the chemical reactivity of several small-molecule compounds to dsDNA's minor groove, covalently bonded polyamide samples were used. PNA and DNA were also used to construct antisense and antigen hybrids, with Watson–Crick or Hoogsteen base pairing with major groove nucleobases giving sequence recognition. Click chemistry created chimeric AMN-TFOs with desirable focused effects and negligible off-target cleavage. Clip-Phen-modified TFOs, 230 polypyridyl-modified TFOs, 232 and intercalating phenanthrene-modified TFOs are three contemporary instances of copper AMN–TFOs. All three systems have distinct advantages in maintaining the desired 2:1 phenthroline/copper ratio for DNA cleavage (clip-Phen TFOs), caging the copper center and facilitating efficient ROS-mediated strand scission (polypyridyl-modified TFO) and improving triplex stability (polypyridyl-modified TFO) (phenanthrene-TFOs). Cerium (IV)/EDTA complexes, recently shown to bind and hydrolytically cleave ssDNA/dsDNA junctions and used in conjunction with PNA to successfully introduce genome changes in vitro and in vivo, are another important class of targeted chemical nucleases. The chemical reactivity and wide flexibility of metal complex design, combined with their coupling to sequence specific samples for directed applications, show that these compounds have a wide range of untapped applications in biological fields such as chemotherapy, protein engineering, DNA footprinting, and gene editing. Parallel advancements in cell and tissue targeting will be essential to maximise their therapeutic potential, either by using specific ligands or creating new targeting modalities.

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