Chronic Effects of Andrographis paniculata Chloroform Extract in Spontaneously Hypertensive Rats

This study was undertaken to investigate the effects of chronic administration of chloroform extract of Andrographis paniculata, known to possess some cardioprotective action, on endothelial dysfunction using isolated spontaneously hypertensive (SH) rat thoracic aorta. Verapamil hydrochloride was used as a positive control to compare its effect on endothelial dysfunction to that of Andrographis paniculata chloroform extract (APCE). HPLC study of APCE was performed and compared with that of the standards, andrographolide (ANG), and 14deoxyandrographolide (DA). Adult male SH rats were treated with 25, 50 and 100 mg/kg APCE and 12.5 mg/kg Verapamil (p.o.) once a day for four weeks. There was a significant (P<0.05) reduction in tail-cuff systolic blood pressure (SBP) measurements in conscious animals treated with 50 and 100 mg/kg APCE as well as in those treated with Verapamil. Similarly, these groups showed endothelium-dependent relaxation to acetylcholine (ACh). Animals treated with APCE 100 mg/kg and Verapamil hydrochloride 12.5 mg/kg showed endotheliumindependent relaxation to sodium nitroprusside (SNP). The findings collectively suggest that chronic treatment with APCE preserves vascular endothelial functions in SH rats. Key words; Acetylcholine, aorta, diterpenoid lactones, endothelium dysfunction, sodium nitro prusside, spontaneously hypertensive rats. INTRODUCTION Andrographis paniculata (F. Acanthaceae) is a medicinal plant in Malaysia which possesses potent effects in treating diabetes and hypertension. (Ahmad and Asmawi, 1993). Studies have shown that Andrographis paniculata (AP) has therapeutic actions on the cardiovascular system (Chang and But, 1987). Water extract obtained from AP produces a significant reduction in systolic blood pressure in both normotensive and SH rats (Zhang, 1996; Tan, 1997). Diterpenoid lactones isolated from AP, namely deoxyandrographolide (DA) and 14-deoxy-11, 12didehydroandrographolide (DDA), have been shown to cause a significant fall in mean arterial blood pressure (MABP) and heart rate. Moreover, these lactones are scientifically proven to non-competitively and dose-dependently antagonize isoproterenol-induced positive chronotropic actions in rat atria (Zhang et al., 1998). In isolated rat thoracic aorta, DA has been observed to alter calcium homeostasis, reduce the contractile response of CaCl2 in the presence of high K and ultimately contribute to vasorelaxation (Zhang and Tan, 1998). Besides AP able to selectively block voltage operated calcium channels and hence inhibiting the calcium influx (Burgos et al., 2000). Vascular endothelial dysfunction is thought to contribute to the development of various cardiovascular disorders such as impairment in coronary circulation and hypertension. (Rubanyi et al., 1993; Luscher et al., 1994). Various mechanisms may be involved in the development of endothelial dysfunction and eventually cardiovascular diseases. Antihypertensive drugs, such as angiotensinconverting enzyme inhibitors, calcium-channel blockers, (Rodrigo et al., 1997; Novosel et al., 1994), and antioxidants are well known to improve endothelial dysfunction (Ulker et al., 2003; Levine et al., 1996). Besides its pharmacological effects on the cardiovascular system, AP possesses other pharmacological activities, such as antipyretic, anti-inflammatory (Deng et.al., 1982), hepatoprotective (Shukla et al., 1992 ; Kapil et al., 1993), immunostimulantory (Puri et al., 1993), and antioxidant actions (Akowuah et al., 2006). Based this background, the main aim of the present study was to investigate the effects of chronic administration of different doses of APCE on systolic blood pressure and vascular function on isolated rat aortas of SH rats. MATERIALS AND METHODS Plant material Fresh aerial parts of Andrographis paniculata were collected from the cultivated nurseries of Malaysian Agriculture Development Institute, Kelantan, Malaysia and authenticated Raghava Naidu Sriramaneni et al /J. Pharm. Sci. & Res. Vol.4(8), 2012, 1924-1928