Cardiovascular Effects of 14-Deoxy-11,12-didehydroandrographolide and Andrographis paniculata Extracts

Abstract

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 β-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.

Key words

Andrographis paniculata - Acanthaceae - 14-deoxy-11,12-didehydroandrographolide - vasorelaxation - chronotropic effects - hypotension

References

• 1 Zhang C Y, Tan B KH. Hypotensive activity of aqueous extract of Andrographis paniculata in rats.  Clin Exp Pharmacol Physiol. 1996;  23 675-8.
• 2 Zhang C Y, Tan B KH. Effects of 14-deoxyandrographolide and 14-deoxy-11,12-didehydroandrographolide on nitric oxide production in cultured human endothelial cells.  Phytother Res. 1999;  13 157-9.
• 3 Puri A, Saxena R, Saxena R P, Saxena K C, Srivastava V, Tandon J S. Immunostimulant agents from Andrographis paniculata .  J Nat Prod. 1993;  56 995-9.
• 4 Shen Y C, Chen C F, Chiou W F. Suppression of rat neutrophil reactive oxygen species production and adhesion by the diterpenoid lactone andrographolide.  Planta Med. 2000;  66 314-7.
• 5 Amroyan E, Gabrielian E, Panossian A, Wikman G, Wagner H. Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced platelet aggregation.  Phytomedicine. 1999;  6 27-31.
• 6 Thisoda P, Rangkadilok N, Pholphana N, Worasuttayangkurn L, Ruchirawat S, Satayavivad J. Inhibitory effect of Andrographis paniculata extract and its active diterpenoids on platelet aggregation.  Eur J Pharmacol. 2006;  553 39-45.
• 7 Zhao H Y, Fang W Y. Antithrombotic effects of Andrographis paniculata Nees in preventing myocardial infarction.  Chin Med J. 1991;  104 770-5.
• 8 Yu B C, Hung C R, Chen W C, Cheng J T. Antihyperglycemic effect of andrographolide in streptozotocin-induced diabetic rats.  Planta Med. 2003;  69 1075-9.
• 9 Zhang X F, Tan B KH. Antihyperglycaemic and antioxidant properties of Andrographis paniculata in normal and diabetic rats.  Clin Exp Pharmacol Physiol. 2000;  27 358-63.
• 10 Chander R, Srivastava V, Tandon J, Kapoor N K. Antihepatotoxic activity of diterpenes of Andrographis paniculata (Kal-Megh) against Plasmodium berghei induced hepatic damage in Mastomys natalensis .  Int J Pharmacog. 1995;  33 135-8.
• 11 Misra P, Pal N L, Guru P Y, Katiyar J C, Srivastava V, Tandon J S. Antimalarial activity of Andrographis paniculata (Kalmegh) against Plasmodium berghei NK 65 in Mastomys natatensis .  Int J Pharmacog. 1992;  30 263-74.
• 12 Zhang C Y, Kuroyangi M, Tan B KH. Cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide in the anaesthetised rat and isolated right atria.  Pharmacol Res. 1998;  38 413-7.
• 13 Zhang C Y, Tan B KH. Vasorelaxation of rat thoracic aorta caused by 14-deoxyandrographolide.  Clin Exp Pharmacol Physiol. 1998;  25 424-9.
• 14 Pholphana N, Rangkadilok N, Thongnest S, Ruchirawat S, Ruchirawat M, Satayavivad J. Determination and variation of three active diterpenoids in Andrographis paniculata (Burm. f.) Nees.  Phytochem Anal. 2004;  15 365-71.
• 15 Matsuda T, Kuroyanagi M, Sugiyama S, Umehara K, Ueno A, Nishi K. Cell differentiation-induced diterpenes from Andrographis paniculata Nees.  Chem Pharm Bull. 1994;  42 1216-25.
• 16 Panossian A, Hovhannisyan A, Mamikonyan G, Abrahamian H, Hambardzumyan E, Gabrielian E. et al . Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human.  Phytomedicine. 2000;  7 351-64.
• 17 Furchgott R F, Zawadzki J V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.  Nature. 1980;  288 373-6.
• 18 Burgos R A, Imilan M, Sánchez N S, Hancke J L. Andrographis paniculata (Nees) selectively blocks voltage-operated calcium channels in rat vas deferens.  J Ethnopharmacol. 2000;  71 115-21.