Vasculoprotective and vasodilatation effects of herbal formula (Sahatsatara) and piperine in spontaneously hypertensive rats.
BACKGROUND
The herbal formula (Sahatsatara, STF), the Thai traditional poly-herbal recipe, has been used for treatment of muscle pain, anti-flatulence and numbness on hands and feet, with the caution when used in hypertensive patients. However, there is no scientific evidence to prove its effects on cardiovascular system. Piperine is the proposed major active compound in STF. It is shown to have antihypertensive effect in the L-NAME-induced endothelial dysfunction rats.


OBJECTIVE
This study investigated the pharmacokinetics, mechanism of action, as well as the hemodynamic and vasoactive effect and toxicity of STF and piperine using spontaneously hypertensive rats (SHR) and normal Wistar rats (NWR).


METHODS
The amount of piperine in STF was measured by ultra performance liquid chromatography (UPLC). SHR and NWR were gavaged with piperine (50mg/kg/day) or STF (100, 300, or 1000mg/kg/day) alone or together with L-NAME (in drinking water) for 28 days. Hemodynamic effects were monitored by noninvasive tail cuff every 7 days. Vasorelaxation effect on the thoracic aorta in organ chamber was observed through force transducer at the end of the experiment. Biochemical parameters for kidney and liver toxicity were measured. In addition, pharmacokinetic study was performed using non-compartment analysis.


RESULTS
The amount of piperine in STF was 1.29%w/w. Both STF and piperine did not affect blood pressure and heart rate in both SHR and NWR. Interestingly, STF and piperine increased acetylcholine-induced vasorelaxation of isolated thoracic aorta and have vascoluprotective effect in nitric oxide (NO) impaired rats. No liver or kidney toxicity was found in this study. Non-compartment pharmacokinetic analysis showed that the time to reach maximum concentration (Tmax) of plasma piperine after administration of piperine and STF were 3.9 and 1.7h, respectively. This result suggested that piperine in the recipe had better absorption than the pure standard piperine.


CONCLUSIONS
STF had no effect on blood pressure in both SHR and NWR. However, it was able to relax isolated thoracic aorta and had the potential for vasculoprotective effect in hypertensive and NO impaired condition. The effects of STF were comparable to those of piperine.
Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Thailand; Department of Applied Thai Traditional Medicine, Faculty of Medicine Siriraj Hospital, Thailand.
Suksalin
S
Booranasubkajorn
Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Thailand.
Sukit
S
Huabprasert
Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Thailand.
Jantanee
J
Wattanarangsan
Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Thailand.
Pruksa
P
Chotitham
Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Thailand.
Pinpilai
P
Jutasompakorn
Department of Applied Thai Traditional Medicine, Faculty of Medicine Siriraj Hospital, Thailand.
Tawee
T
Laohapand
Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Thailand; Department of Applied Thai Traditional Medicine, Faculty of Medicine Siriraj Hospital, Thailand.
Pravit
P
Akarasereenont
Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Thailand. Electronic address: pinpat.tri@mahidol.ac.th.
Pinpat
P
Tripatara
D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D052117:Benzodioxoles / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008517:Phytotherapy; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000737:chemistry*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D013785:Thailand; D014664:Vasodilation / Q000187:drug effects*
D000470:Alkaloids; D000959:Antihypertensive Agents; D052117:Benzodioxoles; D010880:Piperidines; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; C008922:piperine
Hemodynamic; Herbal formula; Hypertension; L-NAME (PubChem CID: 39836); Piperine; Piperine (PubChem CID: 638024); Vasodilatation