Cardiovascular effects of 14-deoxy-11,12-didehydroandrographolide and Andrographis paniculata extracts.
Andrographis paniculata has been widely used as a traditional medicine for the treatment of common cold, diarrhea and hypertension. The three major active diterpenoids are andrographolide (AP1), 14-deoxy-11,12-didehydroandrographolide (AP3) and neoandrographolide (AP4). It has been reported that AP3 has hypotensive and vasorelaxation effects. However, there is only limited information on the cardiovascular effects of the other diterpenoids and crude extracts containing different levels of AP3. Therefore, the present study investigated the effects of these diterpenoids, AP1, AP3, and AP4, isolated from A. paniculata, and different aqueous plant extracts on blood pressure, vascular and chronotropic responses by using conscious rats and their isolated aortas and right atria as the test models. Among the three major diterpenoids, AP3 was the most potent compound for inducing vasorelaxation and decreasing heart rate. In addition, Extract B (high level of AP3) had greater hypotensive effect in conscious rats than Extract A (low level of AP3). Verapamil, a Ca2+ channel blocker, also had a hypotensive effect less than that of Extract C containing a high level of AP3. At the doses and durations of Extract A and B which produced hypotension, the responses of the Extract A-treated aorta to norepinephrine, and the vascular muscarinic responses to acetylcholine of both extracts were decreased. However, repeated doses of both extracts did not alter cardiac beta-adrenoceptor and muscarinic responses of extract-treated rats to NE and ACh, respectively. The results of this study suggest that vascular smooth muscle is the major site of these hypotensive effects of both AP3 and A. paniculata extracts. Furthermore, the consumption of A. paniculata products containing high levels of AP3 may be responsible for causing hypotension in some patients taking this herbal drug.
Yoopan
Nattaporn
N
Toxicology Graduate Programme, Faculty of Science, Mahidol University, Bangkok, Thailand.
Thisoda
Piengpen
P
Rangkadilok
Nuchanart
N
Sahasitiwat
Somjed
S
Pholphana
Nanthanit
N
Ruchirawat
Somsak
S
Satayavivad
Jutamaad
J
D035685:Andrographis; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D008517:Phytotherapy; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
C495626:14-deoxy-11,12-didehydroandrographolide; D000959:Antihypertensive Agents; D004224:Diterpenes; D010936:Plant Extracts