Argemone mexicana extract alleviates gastrointestinal disorders by stimulating muscarinic receptors and blocking voltage-gated L-type calcium channels

Objective: To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods: The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath. The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System. The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis, respectively. Results: The total phenolic and total flavonoids contents of the extract were (267.75 ± 5.77) mg GAE/g and (73.86 ± 6.01) mg QE/g, respectively. Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC50 value of 0.016 mg/mL, which was blocked by atropine (0.3 μM). Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC50 value of 2.185 mg/mL. Furthermore, Argemone mexicana extract relaxed potassium (80 mM)-induced contractions (EC50: 9.07 mg/mL), similar to a standard drug verapamil. The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract (1-5 mg/mL) and verapamil (0.1-1 μM). In addition, the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks. Conclusions: Argemone mexicana shows cholinergic agonist and calcium channel blocker activities, as well as antiemetic effect. It may be used as a potential agent for treating gastrointestinal disorders.

pH-sensitive polyvinylpyrrolidone-acrylic acid hydrogels: Impact of material parameters on swelling and drug release

In this study, we fabricated pH-sensitive polyvinylpyrrolidone/acrylic acid (PVP/AA) hydrogels by a free-radical polymerisation method with variation in the content of monomer, polymer and cross-linking agent. Swelling was performed in USP phosphate buffer solutions of pH 1.2, 5.5, 6.5 and 7.5 with constant ionic strength. Network structure was evaluated by different parameters and FTIR confirmed the formation of cross-linked hydrogels. X-ray crystallography showed molecular dispersion of tramadol HCl. A drug release study was carried out in phosphate buffer solutions of pH 1.2, 5.5 and 7.5 for selected samples. It was observed that swelling and drug release from hydrogels can be modified by changing composition and degree of cross-linking of the hydrogels under investigation. Swelling coefficient was high at higher pH values except for the one containing high PVP content. Drug release increased by increasing the pH of the medium and AA contents in hydrogels while increasing the concentration of cross-linking agent had the opposite effect. Analysis of the drug release mechanism revealed non-Fickian transport of tramadol from the hydrogels.

Nesse estudo, preparamos hidrogéis de polivinilpirrolidona/ácido acrílico(PVP/AA), sensíveis ao pH, por meio de método de polimerização de radical livre, com variações no conteúdo de monômero, de polímero e de agente de ligação cruzada. O inchamento foi realizado em soluções tampão fosfato USP pH 1,2, 5,5, 6,5 e 7,5, com força iônica constante. A estrutura reticular foi avaliada por diferentes parâmetros e o FTIR confirmou a formação de hidrogéis de ligação cruzada. A cristalografia de raios X mostrou dispersão molecular do cloridrato de tramadol. Realizou-se estudo de liberação do fármaco em soluções tampão fosfato pH 1,2, 5,5 e 7,5 para amostras selecionadas. Observou-se que o inchamento e a liberação do fármaco dos hidrogéis podem ser modificados mudando-se a composição e o grau de ligação cruzada dos hidrogéis em estudo. O coeficiente de inchamento foi alto em pH mais altos, exceto para um deles com alto conteúdo de PVP. A liberação do fármaco aumentou com o aumento do pH do meio e do conteúdo em AA nos hidrogéis, enquanto que o aumento na concentração do agente de ligação cruzada apresentou efeito oposto. A análise do mecanismo de liberação do fármaco revelou transporte não Fickiano do tramadol dos hidrogéis.