Potential pharmacodynamic and pharmacokinetic interactions of Nigella Sativa and Trigonella Foenum-graecum with losartan in L-NAME induced hypertensive rats

Abstract

The objective of this investigation was to study whether Nigella Sativa and Trigonella Foenum-graecum, could modulate the losartan pharmacodynamic (PD) and pharmacokinetic (PK) in experimental L-NAME induced hypertensive rats. For in vivo study, the systolic blood pressure (SBP) of rats was measured by the "tail-cuff system" after the treatment of rats with herb alone and herb + losartan in hypertensive rats. The SBP of rats treated with L-NAME + losartan also recorded. For the PK study, blood samples were obtained for up to 12 h to determine the concentrations of the drug, and various PK parameters were calculated. The data displayed that the SBP was significantly (p < 0.05) decreased in the rats when administered with L-NAME + N. Sativa or L-NAME + T. Foenum-graecum in contrast to the rats administered with L-NAME alone. A more prominent decline (p < 0.05) in SBP was detected in rats administered with L-NAME + N. Sativa + losartan and L-NAME + T. Foenum-graecum + losartan. In a PK study, higher losartan C_max and AUC_0-t were noted in rats treated with N. Sativa + losartan and T. Foenum-graecum + losartan, although the difference was not significant in contrast to the control group. This study proposed that the interaction between N. Sativa & losartan and T. Foenum-graecum & losartan could take place on concurrent administration; consequently, the dose of losartan may need to be accustomed when they are utilized simultaneously.

Keywords: L-NAME; Losartan; Nigella Sativa; Pharmacodynamic; Pharmacokinetic; Trigonella Foenum-graecum.

Fig. 1

Tracing of tail-cuff pressure from a rat of (A) L-NAME alone, (B) L-NAME + losartan, and (C) L-NAME + N. Sativa and (D) L-NAME + N. Sativa + losartan treated group using the Visitech blood pressure monitor system.

Fig. 2

Rats systolic blood pressure following oral administration of L-NAME alone, L-NAME + losartan, L-NAME + N. Sativa, and L-NAME + N. Sativa + losartan (n = 5, mean ± SD). *p < 0.05 with respect to L-NAME alone group.

Fig. 3

Tracing of tail-cuff pressure from a rat of (A) L-NAME alone, (B) L-NAME + losartan, and (C) L-NAME + T. Foenum-graecum and (D) L-NAME + T. Foenum-graecum + losartan treated group using the Visitech blood pressure monitor system.

Fig. 4

Rats systolic blood pressure following oral administration of L-NAME alone, L-NAME + losartan, L-NAME + T. Foenum-graecum, and L-NAME + T. Foenum-graecum + losartan (n = 5, mean ± SD). *p < 0.05 with respect to L-NAME alone group.

Fig. 5

Plasma concentration–time profiles of losartan after oral administration of losartan alone or in combination with N. Sativa or T. Foenum-graecum (n = 5, mean ± SE).