Biological Effects Of A Paniculata

A. paniculata has been reported to have multiple pharmacological activities, including the lowering of blood pressure. Anecdotally, it is taken as a bitter infusion from six to seven leaves for lowering very high blood pressure. A published report by Ahmad and Asmawi (12) indicated that the extract of this plant was used among Malays in Malaysia for the treatment of hypertension. Wang and Zhao (13) reported that the extract could alleviate atherosclerotic artery stenosis induced by both deendothelialization and a high-cholesterol diet. This chapter reviews the authors' investigations into the cardiovascular effects of a crude water extract of A. paniculata, its semipurified fractions, and some of its diterpenoid compounds.

The effects of an intraperitoneally administered aqueous extract of A. paniculata on systolic blood pressure (SBP), plasma and lung angiotensin-converting enzyme (ACE) activities, and also the free radical content in the kidneys of male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were also evaluated.

It is well known that ACE plays an important role in blood pressure regulation by (a) catalyzing the conversion of angiotensin I to angiotensin II, which has potent vasoconstrictor effects, and (b) promoting inactivation of the natriuretic vasodilator bradykinin. These actions lead to an elevation in blood pressure. Cushman and Cheung (14) reported that the lungs and kidneys had large amounts of this enzyme.

Suryaprabha et al. (15) reported that in hypertensive states, there is an increased amount of free radicals. Elevated levels of free radicals have in turn been associated with increased amounts of ACE in the kidneys (16). Free radicals, especially superoxide ions, can also inactivate the vasodilators nitric oxide (NO) and prostacyclin (PGI2) (17). All these factors can potentially aggravate the hypertension. We decided to evaluate whether the extract of A. paniculata could affect these parameters and also the blood pressure of the experimental rats.

Chronic intraperitoneal infusion of three different doses of the extract (0.7, 1.4, and 2.8 mg/kg) was administered by osmotic pumps (ALZA Corp., USA) to SHR over 14 days. The extract produced significant dose-dependent reductions in the SBP of SHR compared with vehicle-treated controls. Peak reductions in SBP occurred on day 2 with all three doses (Fig. 3). The lowest of the three doses was thus chosen as the optimum hypotensive dose of the extract.

A follow-up study was done using this optimum dose in SHR and WKY rats. We showed that the extract significantly lowered SBP in both these strains of rats. Plasma but not lung ACE activity in extract-treated SHR was found to be significantly lower than that in vehicle-treated SHR. However, no significant difference was found in plasma and lung ACE activities between extract and vehicle-treated WKY rats.

Interestingly, the kidney TBARS value in vehicle-treated SHR was significantly higher than that in vehicle-treated WKY rats. This appears to be consistent with the expectation that free-radical levels are elevated in hypertension. The level of lipid peroxidation products in the kidneys [as reflected by estimation of thiobarbituric-acid-reacting substance (TBARS)] was also found to be significantly lower in extract-treated SHR but not WKY rats when compared to their corresponding vehicle-treated controls. More recently, it was reported that A. paniculata has antioxidant properties by production of reactive oxygen species (18) or increasing the levels of antioxidant enzymes (19). It will thus have the capacity to reduce free-radical activity. However, the extract was found to lower TBARS content in SHR but not WKY rats. This may be because there are higher levels in the SHR.

Figure 3 Changes in mean systolic blood pressure (SBP) of SHR and WKY rats over a 13-day intraperitoneal infusion of an aqueous extract of A. paniculata (0.7 g/kg) or distilled water. Values shown are the mean ± SEM. SBP of seven animals in each group (except extract-treated SHR, n = 8). *Significantly lower than the vehicle-treated SHR (p = 0.0001, two-way ANOVA). **Significantly lower than the vehicle-treated WKY (p = 0.0001, two-way ANOVA).

Figure 3 Changes in mean systolic blood pressure (SBP) of SHR and WKY rats over a 13-day intraperitoneal infusion of an aqueous extract of A. paniculata (0.7 g/kg) or distilled water. Values shown are the mean ± SEM. SBP of seven animals in each group (except extract-treated SHR, n = 8). *Significantly lower than the vehicle-treated SHR (p = 0.0001, two-way ANOVA). **Significantly lower than the vehicle-treated WKY (p = 0.0001, two-way ANOVA).

It appeared from this initial study that the hypotensive responses to A. paniculata were related neither to the basal level of SBP nor to the strain of rat. The finding that ACE activity was depressed in the plasma but not lungs of extract-treated SHR suggests that the extract may exert its hypotensive effect in SHR by selectively inhibiting the activity of the circulating renin-angioten-sin system. However, no change in either plasma or lung ACE activities occurred in the extract-treated WKY rats, which also had a significant fall in SBP. This suggests that in the normotensive rat, A. paniculata extract may have a different mode of hypotensive action, such as calcium channel blockade, resulting in vascular smooth muscle relaxation, or interaction with the sympathetic nervous system and its receptors at either central or peripheral levels.

Captopril, an ACE inhibitor that is widely used in the treatment of human hypertension, has the ability to scavenge free radicals (20). This could result in the sparing of PGI2 and NO degradation, thus indicating the possibility of a second, and possibly indirect, mode of hypotensive action. Our finding that the hypotensive effect of the A. paniculata extract was associated with reduced ACE activity and reduced kidney lipid peroxidation level indicates some similarity to the effects of captopril.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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