Peperomia pellucida is a plant used in traditional medicine to treat gastric ulcers. Although this gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim herein was to identify the most active compound in the gastroprotective activity of P. pellucida using an ethanol-induced gastric ulcer experimental rat model. A gastroprotective effect was observed when the hexane and dichloromethane extracts were tested, with the higher effect being obtained with the dichloromethane extract (82.3 ± 5.6%) at 100 mg/kg. Dillapiole was identified as the most active compound in this extract. Although there have been previous reports on dillapiole, this is the first on its gastroprotective activity. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 23.1, 56.1, 73.2 and 85.5% gastroprotection, respectively. The effect elicited by dillapiole at 100 mg/kg was not attenuated by pretreatment with indomethacin (10 mg/kg, s.c.), a prostaglandin synthesis blocker, N G -nitro-L-arginine OPEN ACCESSMolecules 2013, 18 11328 methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, or N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of dillapiole does not involve prostaglandins, NO or sulfhydryl groups.

It is known that acute spinal cord injury (SCI) produces hemodynamic alterations, including a reduction in liver blood flow that is more pronounced after high-thoracic than after low-thoracic injury. To determine if these changes have an impact in the pharmacokinetics of high extraction drugs (i.e., those drugs which clearance mainly depends on liver blood flow), we studied the pharmacokinetics of a model compound, phenacetin, and of its main metabolite, acetaminophen, in rats 24 h after a high (T1) or a low (T8) SCI, as well as in sham-lesioned controls. After intravenous administration to animals with SCI, reductions in drug clearance and distribution led to an increase in blood concentrations. These alterations were more pronounced after high than after low SCI, as expected from hemodynamic changes. After oral administration, phenacetin blood levels were similar in sham-lesioned and T1-injured animals, but decreased by injury at T8. This is likely due to a reduction in drug absorption which compensates the changes in distribution and elimination induced by injury at T1, whereas it prevails in T8-lesioned animals. Acetaminophen blood concentrations observed after intravenous or oral phenacetin, or after the oral administration of acetaminophen by itself, were increased or reduced, depending on the overall effect of the alterations on absorption, first pass metabolism, distribution and elimination induced by high and low SCI. Results demonstrate that acute SCI significantly alters the pharmacokinetics of high extraction drugs. The outcome of such alterations depends on the level of SCI and on the route of administration.

This work aimed to study the effect of Cuachalalate methanol extract (CME) on the anti-inflammatory activity and pharmacokinetics of diclofenac sodium, a frequently prescribed non-steroidal anti-inflammatory drug (NSAID). The gastroprotective effect of CME on the gastric injury induced by diclofenac was studied in rats. CME showed a gastroprotective effect of 15.7% at 1 mg kg(-1) and 72.5% at dose of 300 mg kg(-1). Omeprazole, used as anti-ulcer reference drug, showed gastroprotective effects of 50-89.7% at doses tested (1-30 mg kg(-1)). The value of the 50% effective dose for the anti-inflammatory effect of diclofenac sodium (ED50 = 1.14 +/- 0.23 mg kg(-1)) using carrageenan-induced rat paw oedema model, was not modified by the concomitant administration of 30 or 100 mg kg(-1) of CME. The effect of CME (30, 100 and 300 mg kg(-1), p.o.) on the pharmacokinetics of diclofenac sodium was studied. It was observed that the simultaneous administration of diclofenac sodium and 300 mg kg(-1) of CME decreased significantly the values of Cmax (7.08 +/- 1.42 microg mL(-1)) and AUC (12.67 +/- 2.97 microg h mL(-1)), but not the value of tmax (0.13 (0.1-0.25)h) obtained with the administration of diclofenac alone. The simultaneous administration of 30 or 100 mg kg(-1) of CME did not modify the pharmacokinetic parameters of diclofenac. The experimental findings in rats suggest that CME at doses lower than 100 mg kg(-1) protects the gastric mucosa from the damage induced by diclofenac sodium without altering either the anti-inflammatory activity or the pharmacokinetics of this NSAID.