Protective effect of the solvent extracts of Portulacca oleracea against acidified ethanol induced gastric ulcer in rabbits.

Portulacca oleracea L. has been used for treatment of different ailments. The aim of this study was to investigate the effectiveness and possible mechanism of action involved in the anti gastric ulcerogenic effect of Portulacca oleracea. Methanolic extract & subsequent fractions (100, 200 and 400 mg/kg) of Portulacca oleracea (P. oleracea) were administered orally to experimental rabbits one hour before oral administration of HCl/ethanol (40:60). Anti gastric ulcerogenic potential of P. oleracea was evaluated by assessment of gastric pH, pepsin, free acidity, ulcer index, mucus content and total acidity. For the investigation of possible mechanism of action malondialdehyde (MDA), histamine, and H + K + ATPase content were determined in the stomach homogenate. Histopathological study of stomach tissue was carried out by H&E dye. Ethyl acetate fraction (EAF) of P. oleracea was the most potent fraction among all fractions that exhibited efficient protection against acidified ethanol mediated gastric-ulcer. The ethyl acetate fraction (EAF) significantly increased the pH of gastric juice, while pepsin and histamine was observed to decrease significantly in comparison to acidified ethanol group (***p ≤ 0.001). The EAF showed moderately H + K + ATPase inhibitory activity. Moreover, it was also observed that EAF decreased the malondialdehyde (MDA) level in the stomach tissue homogenate showing antioxidant effect. Histopathological studies showed that among the tested fractions, EAF significantly prevented acidified ethanol induced gastric mucosal damage. These results showed that mechanism of anti gastric ulcerogenic potential of P. oleracea could be associated with the reduction in histamine level, H + K + ATPase inhibition and reduced MDA level.

Antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities of pentacyclic triterpenes isolated from Ziziphus oxyphylla Edgew.

Ziziphus oxyphylla Edgew is in folk use in Pakistan as an analgesic, anti-inflammatory, and liver ailments. Therefore, we have investigated antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities of the isolated compounds (ceanothic acid and zizybrenalic acid) from the chloroform fraction of Z. oxyphylla. Ceanothic acid and zizybrenalic acid showed significant DPPH and H2O2 scavenging activity as compared to control. In the acute toxicity study, ceanothic acid and zizybrenalic acid showed no toxic effects upto 200 mg/kg. The antinociceptive activity shown by ceanothic acid and zizybrenalic acid at 50 mg/kg was 64.28% and 65.35% compared to diclofenac sodium (72.3%) at 50 mg/kg. The percent inhibition of xylene-induced ear edema exhibited by ceanothic acid and zizybrenalic acid at 50 mg/kg was 51.33% and 58.66%, respectively, as compared to diclofenac sodium (72.66%). Both the isolated compounds exhibited inhibition of carrageenan-induced paw edema as compared to control. Hepatoprotection exhibited by zizybrenalic acid was more pronounced than ceanothic acid as observed from the decrease in carbon tetrachloride (CCl4)-induced elevation of serum biomarkers, antioxidant enzymes and lipid peroxidation. Furthermore, zizybrenalic acid produced a marked decline in CCl4-induced prolongation of phenobarbital-induced sleeping duration. Zizybrenalic acid exhibited 55.4 ± 1.37% inhibition of hypotonic solution-induced hemolysis compared to sodium salicylate (75.6 ± 2.15%). The histopathological damage caused by CCl4 was also countered by the administration of ceanothic acid and zizybrenalic acid. Ceanothic acid and zizybrenalic acid exhibited antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities. Zizybrenalic acid exhibited better antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activity than ceanothic acid.

Fabrication of Niclosamide loaded solid lipid nanoparticles: in vitro characterization and comparative in vivo evaluation.

Niclosamide (NCS) is an oral anthelminthic drug having low solubility and hence low bioavailability. Current investigation shows an approach to fabricate solid lipid nanoparticles (SLNs) of NCS and evaluated for pharmaceutical, in vitro and in vivo characterization. NFM-3 showed particle size 204.2 ± 2.2 nm, polydispersity index 0.328 ± 0.02 and zeta potential -33.16 ± 2 mV. Entrapment efficiency and drug loading capacity were 84.4 ± 0.02% and 5.27 ± 0.03%, respectively. Scanning electron microscopy image indicated that particles were nanoranged. DSC and P-XRD results showed change in physicochemical properties of NCS. FT-IR spectra confirmed compatibility between NCS and excipients. The drug release profile showed sustained release (93.21%) of NCS in 12 h. Different kinetic models showed zero-order kinetics and Case-II transport mechanism. Study showed maximum stability at refrigerated temperature. In vivo pharmacokinetic study showed 2.15-fold increase in NCS peak plasma concentration as solid lipid nanoparticle formulation (NFM-3) compared to commercial product while relative bioavailability was 11.08. Results including in vitro and in vivo release studies of NCS confirmed that SLNs system is suitable to improve oral delivery of NCS with increased aqueous solubility, permeability and finally bioavailability.