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Trans fatty acids are specific unsaturated fats found in processed foods that undergo hydrogenation, leading to hepatic disorders such as metabolic-associated fatty liver disease (MAFLD) and conditions like CVD and CKD. The effects of different food samples containing trans fatty acids (elaidic and oleic acid) on the liver, heart, and kidney through antioxidant enzyme activity were investigated in animal models. Liver function tests (ALT, ALP, AST, and LDH), heart biomarker levels (CPK, TC, HDL, LDL, and triglycerides), and kidney biomarker levels (serum creatinine, blood urea nitrogen, and serum uric acid) were examined in serum of rabbits and the histopathology of liver tissues. Results showed that these biomarkers were more elevated in the Mujahid Ghee group than in the normal control, oleic acid, and Kausar Ghee groups. The concentration of antioxidant markers such as peroxidase, glutathione, catalase, thiobarbituric acid reactive substances, and superoxide dismutase were lower in the Mujahid Ghee group. HPLC showed that Mujahid Ghee had the highest quantified value of elaidic acid among all selected samples. Overall, this study demonstrated that elaidic acid in its purest form aggravated MAFLD in rabbit livers and provoked CVK and CVD.
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OBJECTIVE: Berberis lycium is an indigenous plant of Pakistan that is known for its medicinal properties. In the current study, we investigated the anti-Alzheimer's effect of berberine isolated from Berberis lycium. METHODS: Root extract of B. lycium was subjected to acetylcholinesterase inhibition assay and column chromatography for bioassays guided isolation of a compound. The neuroprotective and memory improving effects of isolated compound were evaluated by aluminium chloride induced Alzheimer's disease rat model, elevated plus maze (EPM) and Morris water maze (MWM) tests., Levels of dopamine and serotonin in rats brains were determined using HPLC. Moreover, western blot and docking were performed to determine interaction between berberine and ß-secretase. RESULTS: During fractionation, ethyl acetate and methanol (3:7) fraction was collected from solvent mixture of ethyl acetate and methanol. This fraction showed the highest anti-acetylcholinesterase activity and was alkaloid positive. The results of TLC and HPLC analysis indicated the presence of the isolated compound as berberine. Additionally, the confirmation of isolated compound as berberine was carried out using FTIR and NMR analysis. In vivo EPM and MWM tests showed improved memory patterns after berberine treatment in Alzheimer's disease model. The levels of dopamine, serotonin and activity of antioxidant enzymes were significantly (p<0.05) enhanced in brain tissue homogenates of berberine treated group. This was supported by decreased expression of ß-secretase in berberine treated rat brain homogenates and good binding affinity of berberine with ß-secretase in docking studies. Binding energies for interaction of ß-secretase with berberine and drug Rivastigmine is -7.0 kcal/mol and -5.8 kcal/mol respectively representing the strong interactions. The results of docked complex of secretase with berberine and Rivastigmine was carried out using Gromacs which showed significant stability of complex in terms of RMSD and radius of gyration. Overall, the study presents berberine as a potential drug against Alzheimer's disease by providing evidence of its effects in improving memory, neurotransmitter levels and reducing ß-secretase expression in the Alzheimer's disease model.
Assuntos
Doença de Alzheimer , Berberina , Berberis , Lycium , Fármacos Neuroprotetores , Ratos , Animais , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Berberina/farmacologia , Berberina/uso terapêutico , Berberis/química , Berberis/metabolismo , Cloreto de Alumínio , Lycium/metabolismo , Simulação de Acoplamento Molecular , Rivastigmina/farmacologia , Rivastigmina/uso terapêutico , Acetilcolinesterase/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Dopamina , Metanol , Serotonina/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
In the present research, a rapid, simple and efficient green method is used for the incorporation of silver nanoparticles (AgNPs) into poly(ethylene glycol) methacrylate (PEGMA) to create biocatalysts with excellent properties for pharmaceutical purpose. In the first phase, Caralluma tuberculata capped AgNPs (Ca-AgNPs) were prepared using green synthetic approach and in the second phase Caralluma tuberculata capped AgNPs were hybridized with poly(ethylene glycol) methacrylate to form PEGMA-AgNPs. Both the virgin (naked or uncapped) and polymer-capped materials were characterized spectroscopically and their results were compared. Fourier transform infrared spectroscopy showed no new peak after the capping procedure, showing that only physical interactions takes place during capping. After PEGMA capping, the spectra of the AgNPs red shifted (from 450 nm to 520 nm) and the overall particle size of AgNPs increased. Catalytic activity of the nanoparticles and hybrid system were tested by choosing the catalytic reduction of 4-nitrophenol (4-NP) as a model reaction. Both synthesized NPs and polymer capped NPs exhibits catalytic activity for the reduction of 4-NP to 4-aminophenol. The polymer hybrid exhibits remarkable antiproliferative, antioxidant, cytotoxic, antidiabetic and antileishmanial activities.
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Nanopartículas Metálicas , Prata , Prata/química , Nanopartículas Metálicas/química , Antioxidantes/química , Polietilenoglicóis/química , MetacrilatosRESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disorder typified by several neuropathological features including amyloid-beta (Aß) plaque and neurofibrillary tangles (NFTs). Cholesterol retention and oxidative stress (OS) are the major contributors of elevated ß- and γ-secretase activities, leading to excessive Aß deposition, signifying the importance of altered cholesterol homeostasis and OS in the progression of Aß-mediated neurodegeneration and cognitive deficit. However, the effect of Aß on cholesterol metabolism is lesser-known. In this study, we evaluated the effect of quinovic acid (QA; 50 mg/kg body weight, i.p.) against the intracerebroventricular (i.c.v.) injection of Aß (1-42)-induced cholesterol dyshomeostasis, oxidative stress, and neurodegeneration in the cortex and hippocampal brain regions of wild-type male C57BL/6J mice. Our results indicated that Aß (1-42)-treated mice have increased Aß oligomer formation along with increased ß-secretase expression. The enhanced amyloidogenic pathway in Aß (1-42)-treated mice intensified brain cholesterol accumulation due to increased expressions of p53 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) enzyme. Importantly, we further confirmed the p53-mediated HMGCR axis activation by using pifithrin-α (PFT) in SH-SY5Y cells. Furthermore, the augmented brain cholesterol levels were also associated with increased OS. However, the QA administration to Aß (1-42)-injected mice significantly ameliorated the Aß burden, p53 expression, and cholesterol accumulation by deterring the oxidative stress through upregulating the Nrf2/HO-1 pathway. Moreover, the QA downregulated gliosis, neuroinflammatory mediators (p-NF-κB and IL-1ß), and the expression of mitochondrial apoptotic markers (Bax, cleaved caspase-3, and cytochrome c). QA treatment also reversed the deregulated synaptic markers (PSD-95 and synaptophysin) and improved spatial learning and memory behaviors in the Aß-treated mouse brains. These results suggest that Aß (1-42) induces its acute detrimental effects on cognitive functions probably by increasing brain cholesterol levels through a possible activation of the p53/HMGCR axis. However, QA treatment reduces the cholesterol-induced oxidative stress, neuroinflammation, and neurodegeneration, leading to the restoration of cognitive deficit after Aß (1-42) i.c.v. injection in mice.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Colesterol/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos , Triterpenos/farmacologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/toxicidadeRESUMO
Selective GLP-1 secretagogues represent a novel potential therapy for type 2 diabetes mellitus. This study examined the GLP-1 secretory activity of the ethnomedicinal plant, Fagonia cretica, which is postulated to possess anti-diabetic activity. After extraction and fractionation extracts and purified compounds were tested for GLP-1 and GIP secretory activity in pGIP/neo STC-1 cells. Intracellular levels of incretin hormones and their gene expression were also determined. Crude F. cretica extracts stimulated both GLP-1 and GIP secretion, increased cellular hormone content, and upregulated gene expression of proglucagon, GIP and prohormone convertase. However, ethyl acetate partitioning significantly enriched GLP-1 secretory activity and this fraction underwent bioactivity-guided fractionation. Three isolated compounds were potent and selective GLP-1 secretagogues: quinovic acid (QA) and two QA derivatives, QA-3ß-O-ß-D-glycopyranoside and QA-3ß-O-ß-D-glucopyranosyl-(28â1)-ß-D-glucopyranosyl ester. All QA compounds activated the TGR5 receptor and increased intracellular incretin levels and gene expression. QA derivatives were more potent GLP-1 secretagogues than QA. This is the first time that QA and its naturally-occurring derivatives have been shown to activate TGR5 and stimulate GLP-1 secretion. These data provide a plausible mechanism for the ethnomedicinal use of F. cretica and may assist in the ongoing development of selective GLP-1 agonists.
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Células Enteroendócrinas/efeitos dos fármacos , Polipeptídeo Inibidor Gástrico/agonistas , Peptídeo 1 Semelhante ao Glucagon/agonistas , Hipoglicemiantes/farmacologia , Proglucagon/agonistas , Zygophyllaceae/química , Linhagem Celular , Células Enteroendócrinas/citologia , Células Enteroendócrinas/metabolismo , Polipeptídeo Inibidor Gástrico/biossíntese , Polipeptídeo Inibidor Gástrico/genética , Polipeptídeo Inibidor Gástrico/metabolismo , Regulação da Expressão Gênica , Peptídeo 1 Semelhante ao Glucagon/biossíntese , Peptídeo 1 Semelhante ao Glucagon/genética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Humanos , Hipoglicemiantes/isolamento & purificação , Incretinas/agonistas , Incretinas/genética , Incretinas/metabolismo , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proglucagon/biossíntese , Proglucagon/genética , Pró-Proteína Convertases/genética , Pró-Proteína Convertases/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
Traditional medicinal plants are often used for both the prevention and the treatment of local diseases. Taking into consideration the medicinal importance of Hedera nepalensis within local Pakistani traditions, the present study was undertaken to analyze the in vitro cancer chemopreventive and cytotoxic properties of the plant. The in vitro cancer chemopreventive testing was performed using nitrite assay, NFκB assay, aromatase assay, and quinone reductase 1 (QR1) assay. The cytotoxic potential was evaluated on three cancer-cell lines: MCF-7, MDA-MB-231, and HeLa using sulforhodamine B (SRB) assay. The results of cancer chemopreventive assays show that n-hexane and ethyl acetate fractions of tested plant have promising cancer chemopreventive potential. Lupeol isolated from n-hexane as well as ethyl acetate fraction showed lowest IC50 (0.20 ± 1.9 µM) in NFκB assay. Crude extract and its fractions inhibited the growth of three cancer cell lines by more than 60%, IC50 value of lupeol varied from 2.32 to 10.2 µM. HPLC-DAD-based quantification of lupeol in different plant tissues demonstrated that leaves of H. nepalensis are a rich source of lupeol (0.196 mg/100 mg dry weight). Our data have shown that H. nepalensis harbors cancer chemopreventive and cytotoxic agents.
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Anticarcinógenos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Hedera/química , Neoplasias/tratamento farmacológico , Triterpenos Pentacíclicos/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Anticarcinógenos/isolamento & purificação , Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Células HeLa , Humanos , Células MCF-7 , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Plantas MedicinaisRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The two plants investigated here (Fagonia cretica L. and Hedera nepalensis K. Koch) have been previously reported as natural folk medicines for the treatment of diabetes but until now no scientific investigation of potential anti-diabetic effects has been reported. MATERIALS AND METHODS: In vitro inhibitory effect of the two tested plants and their five isolated compounds on the dipeptidyl peptidase 4 (DPP-4) was studied for the assessment of anti-diabetic activity. RESULTS: A crude extract of Fagonia cretica possessed good inhibitory activity (IC50 value: 38.1 µg/ml) which was also present in its n-hexane (FCN), ethyl acetate (FCE) or aqueous (FCA) fractions. A crude extract of Hedera nepalensis (HNC) possessed even higher inhibitory activity (IC50 value: 17.2 µg/ml) and this activity was largely retained when further fractionated in either ethyl acetate (HNE; IC50: 34.4 µg/ml) or n-hexane (HNN; 34.2 µg/ml). Bioactivity guided isolation led to the identification of four known compounds (isolated for the first time) from Fagonia cretica: quinovic acid (1), quinovic acid-3ß-O-ß-D-glycopyranoside (2), quinovic acid-3ß-O-ß-D-glucopyranosyl-(28â1)-ß-D-glucopyranosyl ester (3), and stigmasterol (4) all of which inhibited DPP-4 activity (IC50: 30.7, 57.9, 23.5 and >100 µM, respectively). The fifth DPP-4 inhibitor, the triterpenoid lupeol (5) was identified in Hedera nepalensis (IC50: 31.6 µM). CONCLUSION: The experimental study revealed that Fagonia cretica and Hedera nepalensis contain compounds with significant DPP-4 inhibitory activity which should be further investigated for their anti-diabetic potential.
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Inibidores da Dipeptidil Peptidase IV/farmacologia , Hedera , Hipoglicemiantes/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Zygophyllaceae , Inibidores da Dipeptidil Peptidase IV/química , Hipoglicemiantes/química , Medicina Tradicional/métodosRESUMO
A carboxylic acid ligand, (Z)-4-(4-acetylphenylamino)-4-oxobut-2-enoic acid (APA-1), and its triphenyl-(APA-2) and tributyl-tin(IV) (APA-3) compounds have been synthesized and investigated for their binding with ds.DNA using UV-visible spectroscopy, fluorescence spectroscopy, cyclic voltammetry, and viscosity measurements under physiological conditions of pH and temperature. The experimental results from all techniques i.e. binding constant (Kb), binding site size (n) and free energy change (ΔG) were in good agreement and inferred spontaneous compound-DNA complexes formation via intercalation. Among all the compounds APA-3 showed comparatively greater binding at pH 4.7 as evident from its greater Kb values {APA-3: Kb: 5.63×10(4)M(-1) (UV); 7.94×10(4)M(-1) (fluorescence); 9.91×10(4)M(-1) (CV)}. Electrochemical processes of compounds before and after the addition of DNA were found diffusion controlled. Among all compounds, APA-3 exhibited best antitumor activity.
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Antineoplásicos/química , Complexos de Coordenação/química , DNA/química , Compostos Orgânicos de Estanho/química , Agrobacterium tumefaciens , Antineoplásicos/farmacologia , Ácidos Carboxílicos/química , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Eletroquímica , Ligantes , Compostos Orgânicos de Estanho/farmacologia , Tumores de Planta/etiologia , Solanum tuberosum , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , ViscosidadeRESUMO
We report the synthesis, characterization, biological evaluation and quantitative structure-activity relationship of some Schiff base esters as promising new antitumor, antioxidant and anti-inflammatory agents. The Schiff base esters were synthesized by two synthetic routes using variably substituted hydroxy benzaldehydes with para amino phenol in appreciable yields. All the newly synthesized esters have been characterized by (1)H-NMR,(.13)C-NMR, FT-IR techniques and elemental analysis. The synthesized esters were examined for antioxidant, antitumor and anti-inflammatory potentials through different bioassays and quantitative structure-activity relationship was studied. Bioassays showed encouraging results and indicated that some of these title compounds may have potential for further pharmacological investigations.
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Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antioxidantes/síntese química , Antioxidantes/farmacologia , Ésteres/síntese química , Ésteres/farmacologia , Bases de Schiff/síntese química , Bases de Schiff/farmacologia , Animais , Carragenina , Dano ao DNA , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/prevenção & controle , Feminino , Espectroscopia de Ressonância Magnética , Masculino , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Tumores de Planta/microbiologia , Relação Quantitativa Estrutura-Atividade , Ratos , Solanum tuberosum/efeitos dos fármacos , Solanum tuberosum/microbiologia , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Ni(II), Cu(II) and Zn(II) metal complexes of N-phthaloylglycine were synthesized, characterized, reported for single crystal X-ray diffraction analysis for Ni(II) complex, and investigated for their binding with DNA under physiological conditions, using spectroscopic (UV-visible and fluorescence) and hydrodynamic techniques. Experimental results from both spectroscopic methods were comparable and further supported by viscosity measurements. Binding constant "K(b)" obtained from both spectroscopic methods revealed significant binding of compounds with DNA via intercalation. Among all compounds comparatively good DNA binding was found for Zn(II) complex. Free energies of compounds-DNA interactions indicated spontaneity of their binding. Dynamic and bimolecular enhancement values disclose static process involved in compounds-DNA complex formation. All compounds exhibited broad range antibacterial, while Zn(II) complex exhibited best antitumor activity.
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DNA/metabolismo , Glicina/análogos & derivados , Compostos Organometálicos/síntese química , Compostos Organometálicos/metabolismo , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Bioensaio , Compostos de Bifenilo/química , Técnicas de Química Sintética , Cobre/química , Cristalografia por Raios X , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/metabolismo , Sequestradores de Radicais Livres/farmacologia , Fungos/efeitos dos fármacos , Glicina/química , Concentração de Íons de Hidrogênio , Níquel/química , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Picratos/química , Temperatura , Zinco/químicaRESUMO
Interaction and binding of isonicotinic acid hydrazide (INH) and its two analogs; pyrazine carboxylic acid hydrazide (PCH) and 2,4-dihydroxy benzoic acid hydrazide (2,4-DHBAH) with DNA has been investigated by UV-spectroscopy and cyclic voltammetry (CV) at physiological conditions of pH and temperature. Experimental results from both techniques were in good agreement and indicated stronger binding and formation of hydrazides-DNA complexes via intercalation. Among three hydrazides, 2,4-DHBAH showed greater interaction toward DNA at stomach pH (4.7) as evident from its comparatively greater binding constant, {K(b); 2.02 × 10(4) M(-1) (UV), 3.13 × 10(4) M(-1) (CV)}. The greater binding site size (n = 3) for 2,4-DHBAH at stomach pH inferred 3:1 binding stoichiometry and possibility of electrostatic interactions or hydrogen bonding along with intercalative mode of interaction between 2,4-DHBAH and DNA. The free energies of hydrazides-DNA complexes indicated the spontaneity of their binding. 2,4-DHBAH has shown promising anti-bacterial activities while anti-oxidant and cytotoxic potentials were exhibited by all three hydrazides.