Study on the intervention effects of Pinggan Prescription () on spontaneously hypertensive rats based on metabonomic combined with pharmacodynamic methods.

OBJECTIVE: To investigate the effects of Pinggan Prescription (, PGP) on hypertension by the associated methods of metabonomic and pharmacodynamic.

METHODS: A total of 32 male spontaneously hypertensive rats (SHRs) were randomly divided into two groups by using the random number table method: a treatment group (n=18) and a model group (n=14). The Wistar rats (n=14) were used as the normal group. Different prescription were used to intervene three groups: the treatment group in which PGP extract was administered orally at a dose of 18.336 g/kg (PGP/body weight), and the model group in which physiological saline was administered at the equivalent dose. The same treatment was applied to the normal group as the model group. The blood pressure was measured by tail-cuff method, and pharmacodynamic indexes including cyclic adenosine monophosphate (cAMP) and angiotensinII (Ang II) were tested by enzyme-linked immunosorbent assay. The plasma samples from three groups were detected by gas chromatography-mass spectrometry (GC-MS).

RESULTS: Compared with the model group, blood pressure of treatment group was obviously reduced after continuous curing with PGP (P<0.01). The pharmacodynamic results illustrated that the content of Ang II increased with the raised blood pressure and the cAMP expressed the converse trend. After curing with PGP, the content of Ang II decreased, the difference between model group and treatment group was significant (P<0.01), and the cAMP expressed the converse trend. Five potential biomarkers were identified, including arachidonic acid, hexadecanoic acid, elaidic acid, octadecanedioic acid and 9,12-octadecadienoic acid. These metabolites had shown significantly change as followed: arachidonic acid, hexadecanoic acid and elaidic acid were significantly higher in the model group than those in the normal group, but lower levels of octadecanedioic acid and 9,12-octadecadienoic acid. After the treatment of PGP, the metabolites above all had the trends of returning to normal combined with the reduced blood pressure.

CONCLUSIONS: PGP intervention in hypertension played a major role in the metabolism of arachidonic acid and linoleic acid. Metabonomic combined with pharmacodynamic methods could be potentially powerful tools to investigate the mechanism of Chinese medicine.