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BACKGROUND: Cucurbita pepo (C. pepo) is cultivated and used traditionally as vegetable as well as medicine in different parts of the world. The aim of current study was to investigate the potential of C. pepo in attenuation of diabetic neuropathy via using streptozotocin (STZ)-induced diabetes model in male wistar rats. MATERIALS AND METHODS: Diabetic neuropathy was induced by administration of STZ; 65 mg/kg, i.p. and Nicotinamide (NAD; 230 mg/kg i.p.) and assessed by measuring thermal hyperalgesia, mechanical hyperalgesia and motor nerve conduction velocity (MNCV) in experimental animals. Treatment with different doses of (100, 200 and 400 mg/kg, p.o.) petroleum ether extract of C. pepo (CPE) and hydroethanolic extract of C. pepo (CHE) was started from the 60th day of STZ/NAD administration and continued upto 90th day. RESULTS: CPE and CHE significantly attenuated the behavioural changes including hyperalgesia, allodynia and MNCV linked to diabetic neuropathy. Moreover, the oxidative stress and level of TNF-α, TGF-ß and IL-1ß was found to be significantly attenuated in experimental animals. CONCLUSION: Thus C. pepo might ameliorate the progression of diabetic neuropathy via modulation of chronic hyperglycemia and therefore and have therapeutic potential for treatment of diabetic neuropathic pain.
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Cucurbita , Diabetes Mellitus Experimental , Neuropatías Diabéticas , Ratas , Masculino , Animales , Neuropatías Diabéticas/inducido químicamente , Neuropatías Diabéticas/tratamiento farmacológico , Hiperalgesia/tratamiento farmacológico , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , NAD , Estrés Oxidativo , Ratas Wistar , InflamaciónRESUMEN
BACKGROUND: Polysaccharides decrease the glucose level by inhibiting α-glucosidase enzyme which further increases the level of GLP-1 (Glucagon-like peptide 1) to increase the insulin level as per earlier reports. OBJECTIVE: Similar hypothesis was designed in present study to investigate the α-glucosidase enzyme inhibition and involvement of GLP-1 in antidiabetic mechanism of Acacia tortilis polysaccharides (AEATP) in diabetic rats. Isolated polysaccharides were analyzed for their chemical nature by using HPLC and FTIR method. MATERIALS AND METHODS: Male albino wistar rats were divided into control, diabetic, diabetic + voglibose, diabetic + glimepiride, diabetic+250, 500, 1000 mg/kg of AEATP, diabetic + glimepiride + voglibose, diabetic + glimepiride+ 250, 500 and 1000 mg/kg AEATP, diabetic + GLP-1 antagonist+250, 500 and 1000 mg/kg AEATP. Plasma glucose, insulin and active GLP-1 levels were measured 15 min after OGTT. Fasting blood glucose, Plasma triglycerides, glycated hemoglobin (HbA1c), Fasting insulin, pancreatic insulin content, ileum and colon GLP-1 content were assessed at 5th week. Association of alpha-glucosidase was also assessed with GLP-1 and insulin. RESULTS: AEATP significantly attenuated hyperglycemia by increasing insulin level in plasma and pancreas and increased active GLP-1 as well as insulin level in diabetic rats after OGTT. GLP-1 content was significantly increased in ileum and colon by inhibiting alpha-glucosidase. Involvement of GLP-1 in antihyperglycemic effect of AEATP was confirmed by using GLP-1 antagonist. Moreover, AEATP significantly improved dyslipidemia in diabetic rats. HPLC analysis of A. tortilis polysaccharide comprised four specific monosaccharides (Rhamnose, Glucuronic acid, glucose and galactose) and FTIR spectrum shown band at 3430.6 cm-1 (O-H stretching), 2940.3 cm-1 (C-H linkage), 1630.4 cm-1 (carbonyl stretching), 1410 cm-1 (uronic acid) and 1030.5 cm-1 (glycosidic linkage). CONCLUSION: It can be concluded that antidiabetic effect of AEATP is through the modulation of GLP-1 level in plasma and intestinal tissue via alpha glucosidase inhibition.
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ETHNOPHRAMACOLOGICAL RELEVANCE: Coriandrum sativum L. is traditionally acknowledged for its use in inflammatory disorders, altered blood lipid levels, respiratory and digestive problems. AIM OF THE STUDY: The present study investigates possible role of hydro-alcoholic extract of C. sativum (CHA) seeds in the attenuation of indices of diabetic peripheral neuropathy (DPN). MATERIALS AND METHODS: Phytochemical analysis was carried out by employing chromatographic, spectroscopic as well as spectrometric techniques. Diabetes was induced by a single i.p. injection of freshly prepared STZ (65â¯mg/kg). The indexed markers of DPN, i.e., thermal and mechanical hyperalgesia were found to be prominent on the 60th day of STZ administration. Administration of CHA (100, 200, and 400â¯mg/kg, p.o.) for 30 days was started on the substantiation of DPN onset. Molecular docking study was performed by targeting TNF-α. RESULTS: Phytochemical analysis revealed the presence of flavonoids, terpenoids, and phenolic acids. Oral administration of CHA considerably attenuated hyperglycemia and decreased pain threshold in diabetic rats as well as modulated oxidative-nitrosative stress. Docking study suggested good affinity of flavonoids when docked into the binding site of TNF-α. CONCLUSION: In conclusion, using STZ model, it was successfully predicted that CHA might be beneficial in diabetes-induced neuropathic pain by inhibiting oxidative/nitrosative stress and inflammatory cytokine.
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Coriandrum , Neuropatías Diabéticas/tratamiento farmacológico , Neuronas/efectos de los fármacos , Estrés Nitrosativo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/patología , Relación Dosis-Respuesta a Droga , Masculino , Neuronas/metabolismo , Neuronas/patología , Estrés Nitrosativo/fisiología , Estrés Oxidativo/fisiología , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Inthe present study, we have demonstrated the phytochemical composition of petroleum ether extract of C. sativum (CPE) seeds by using chromatographic, spectroscopic as well spectrometric analysis. CPE was evaluated for its possible role in mitigation of diabetic nephropathy (DN) in Streptozotocin (STZ)-nicotinamide (NAD) induced type 2 diabetes model. Administration of CPE at doses of 100, 200, and 400 mg/kg for 45 days has produced significant attenuation of elevated biochemical parameters including serum glucose, lipid and creatinine levels. CPE has also reserved albuminuria and elevated creatinine clearance in treated diabetic rats. Advanced glycation end products (AGEs) formation in kidneyswas also considerably reduced along with noteworthy increase in level of superoxide dismutase (SOD), glutathione (GSH), and decrease in lipid peroxidation in terms of thiobarbituric acid reactive species (TBARS). Molecular docking studies were also employed to reveal out the possible mechanism. In conclusion, using STZ-NAD model, we have successfully predicted that by assets of bioactive constituents CPE might inhibit the progression of DN. C. sativum may act as potential adjuvant for antidiabetic therapy and needs to be investigated further.
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Coriandrum/química , Nefropatías Diabéticas/patología , Productos Finales de Glicación Avanzada/metabolismo , Extractos Vegetales/química , Animales , Sitios de Unión , Glucemia/análisis , Coriandrum/metabolismo , Creatinina/sangre , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Cromatografía de Gases y Espectrometría de Masas , Glutatión/metabolismo , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Peroxidación de Lípido/efectos de los fármacos , Lípidos/sangre , Masculino , Simulación del Acoplamiento Molecular , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Wistar , Semillas/química , Semillas/metabolismo , Superóxido Dismutasa/metabolismo , Terpenos/análisis , Terpenos/farmacología , Terpenos/uso terapéuticoRESUMEN
Traditional herbal medicines are attaining more popularity and are being widely practiced. Coriandrum sativum L. is one of the oldest herbal medicinal plants valued for its nutritional and medicinal properties. Present investigation was focussed on evaluation of attenuating potential of flavonoid rich extract of C. sativum (FCS) seeds against pathogenic markers of diabetic complications i.e. advanced glycation end products (AGEs), sorbitol and aldose reductase (ALR); by using in-vitro methods. Gas chromatography-mass spectrometry (GC-MS) and Infrared spectroscopy of FCS revealed the presence of different flavonoids. Results demonstrated that FCS has produced 79.80% inhibition of AGEs formation. Additionally, FCS was effective against sorbitol accumulation and ALR inhibition with IC50 values of 221 µg/ml and 6.08 µg/ml respectively. Molecular docking was conducted against three binding site for ALR, RAGEs and sorbitol dehydrogenase to explore their binding interactions with identified flavonoids. The constituents F2, F4 and F6 have shown good binding interactions with all the receptors. The visualisation of the docked complexes revealed the occurrence of hydrophobic forces and hydrogen bonding in receptor and docked constituents. The results were in support with experimental inhibitory activities of FCS against these biomarkers and provide a considerable basis for the identification and development of new inhibitors.
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Herbal medicines have become a core interest, and they are used widely. Lagenaria siceraria is known for its antihyperglycemic, antidyslipidemic, antioxidant potential, and the present study was designed to explore the possible role of L. siceraria in attenuation of diabetic complications via in vitro modulation of advanced glycation end products (AGEs), sorbitol, and aldose reductase (ALR)-three major biomarkers of diabetic complications. To the best of our knowledge, no study has yet been carried out to explore L. siceraria to inhibit these biomarkers. Hydroalcohol extract of L. siceraria (LHA) was evaluated for its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide, nitric oxide, and superoxide radicals, total antioxidant capacity, and reducing-power assay. Antiglycation activity was carried out by bovine serum albumin (BSA) fluorescence method. Sorbitol accumulation was evaluated in red blood cells (RBCs) and ALR1 was obtained from kidney of rat to carry out the study. Quercetin was also quantified by high-performance liquid chromatography (HPLC) analysis with 14.3 mg per 100 g of LHA. LHA exhibited 854 mg/g gallic acid equivalent of phenol content and 104 mg/g quercetin equivalent of flavonoids and was found to be significantly active against the antioxidant assays evaluated. LHA has shown 80.12% inhibition of AGE formation. LHA was found to be effective against sorbitol accumulation and ALR1 inhibition with IC50 198.25 µg/ml and 6.24 µg/ml, respectively. These results reveal that LHA may exert beneficial effects against diabetic complications by its antioxidant and antiglycation potential.
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Aldehído Reductasa/antagonistas & inhibidores , Cucurbitaceae/química , Complicaciones de la Diabetes/tratamiento farmacológico , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Extractos Vegetales/farmacología , Sorbitol/antagonistas & inhibidores , Aldehído Reductasa/química , Animales , Antioxidantes/farmacología , Biomarcadores , Eritrocitos/química , Etanol , Depuradores de Radicales Libres , Frutas/química , Productos Finales de Glicación Avanzada/química , Glicosilación/efectos de los fármacos , Humanos , Riñón/enzimología , Masculino , Plantas Medicinales , Ratas , Sorbitol/sangre , Sorbitol/química , AguaRESUMEN
Mannich bases are the end products of Mannich reaction and are known as beta-amino ketone carrying compounds. Mannich reaction is a carbon-carbon bond forming nucleophilic addition reaction and is a key step in synthesis of a wide variety of natural products, pharmaceuticals, and so forth. Mannich reaction is important for the construction of nitrogen containing compounds. There is a number of aminoalkyl chain bearing Mannich bases like fluoxetine, atropine, ethacrynic acid, trihexyphenidyl, and so forth with high curative value. The literature studies enlighten the fact that Mannich bases are very reactive and recognized to possess potent diverse activities like anti-inflammatory, anticancer, antifilarial, antibacterial, antifungal, anticonvulsant, anthelmintic, antitubercular, analgesic, anti-HIV, antimalarial, antipsychotic, antiviral activities and so forth. The biological activity of Mannich bases is mainly attributed to α, ß-unsaturated ketone which can be generated by deamination of hydrogen atom of the amine group.
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Hydrazones are a special class of organic compounds in the Schiff base family. Hydrazones constitute a versatile compound of organic class having basic structure (R1R2C=NNR3R4). The active centers of hydrazone, that is, carbon and nitrogen, are mainly responsible for the physical and chemical properties of the hydrazones and, due to the reactivity toward electrophiles and nucleophiles, hydrazones are used for the synthesis of organic compound such as heterocyclic compounds with a variety of biological activities. Hydrazones and their derivatives are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal, anti-HIV, and so forth. The present review summarizes the efficiency of hydrazones as potent anti-inflammatory agents.
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We report the synthesis and biological assessment of 1,3,4-oxadiazole substituted 24 derivatives as novel, potential antibacterial agents. The structures of the newly synthesized derivatives were established by the combined practice of UV, IR, (1)H NMR, (13)C NMR, and mass spectrometry. Further these synthesized derivatives were subjected to antibacterial activity against all the selected microbial strains in comparison with amoxicillin and cefixime. The antibacterial activity of synthesized derivatives was correlated with their physicochemical and structural properties by QSAR analysis using computer assisted multiple regression analysis and four sound predictive models were generated with good R(2), R(adj)(2), and Fischer statistic. The derivatives with potent antibacterial activity were subjected to molecular docking studies to investigate the interactions between the active derivatives and amino acid residues existing in the active site of peptide deformylase to assess their antibacterial potential as peptide deformylase inhibitor.
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Antiinfecciosos/química , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Oxadiazoles/química , Oxadiazoles/farmacología , Amidohidrolasas/química , Aminoácidos/química , Amoxicilina/farmacología , Dominio Catalítico , Cefixima/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
A series of benzamide substituted Mannich bases (1-7) were synthesized. The synthesized derivatives were authenticated by TLC, UV-Visible, FTIR, NMR, and mass spectroscopic techniques and further screened for in vitro antibacterial activity by test tube dilution method using amoxicillin and cefixime as standard drugs. The compounds 5, 6, and 7 were found to be the most active antibacterial agents among all the synthesized compounds. The physicochemical similarity of the compounds with standard drugs was assessed by calculating various physicochemical properties using software programs. The percent similarity of synthesized compounds was found to be good and compound 1 was found to have higher percentage of similarity. The compounds were subjected to QSAR by multilinear regression using Analyze it version 3.0 software, and four statistically sound models were developed with R2 (0.963-0.997), Radj2 (0.529-0.982), and Q2 (0.998-0.999) with good F (2.35-65.56) values.