The effects of Eurycoma longifolia JACK were studied on the orientation activities of sexually experienced male rats towards receptive females (mounting, licking, anogenital sniffing), environment (exploration, raring, climbing), themselves (genital grooming, non-genital grooming) and mobility (unrestricted, restricted) after dosing them with 200, 400 and 800 mg/kg body weight twice daily for 10 d prior to the test. The results showed that E. longifolia JACK modified the orientation activities of the treated male rats in that they significantly displayed more frequent and vigorous mounting, licking and anogenital sniffing towards the receptive females, and it further intensified self orientation as indicated by the increased grooming of the genitals compared to the controls (p<0.05). In addition, rats treated with 800 mg/kg of methanol, water and butanol extracts of E. longifolia JACK continued to show confinement to a particular area of the cage (around the female), thus showing restriction in movement as compared to the controls (p<0.05). However, the treated males possessed a lack of interest in the external environment as indicated by a reduction in exploration, raring and climbing on the cage wall. Hence, the present study further supports the folk use of E. longifolia JACK as an aphrodisiac.
The effects of Eurycoma longifolia Jack were studied on the libido of sexually experienced male rats after dosing them with 200, 400 and 800 mg/kg body weight twice daily of different fractions of E. longifolia Jack for 10 days. Results showed that E. longifolia Jack produced a dose-dependent increase in mounting frequency of the treated animals with 400 mg/kg of chloroform, methanol, water and butanol fractions resulting in mounting frequencies of 5.3 +/- 1.2, 4.9 +/- 0.7, 4.8 +/- 0.7 and 5.2 +/- 0.1, and 800 mg/kg further increased them to 5.4 +/- 0.8, 5.4 +/- 0.8, 5.2 +/- 0.6 and 5.3 +/- 0.2 respectively but there were no erections, intromissions, ejaculations or seminal emissions during the 20-min observation period which allowed for the measurement of sexual arousal reflected by mounting frequency uninfluenced by other behavioural components. This study provides evidence that E. longifolia Jack is a potent stimulator of sexual arousal in sexually vigorous male rats in the absence of feedback from genital sensation.
The effects ofEurycoma longifolia Jack were studied on the sexual behaviour of male rats. Sexually normal male rats were treated twice daily with 500 mg kg(-1) of different fractions ofE. longifolia Jack for 10 days prior to test and were then observed for their copulatory behaviour with a receptive female in a copulation cage. Results showed that was a significant increase (p<0.05) in EL-1, EL-2, EL-3 but significant decrease (p<0.05) in both PEI-1 and PEI-2 in treated male rats as compared to the control male rats indicating thatE. longifolia Jack increased the sexual performance of the treated male rats by extending the duration of coitus and decreasing the refractory period between the different series of copulation. Hence, this preliminary work supports the folk use of this plant as having aphrodisiac property.
The aim of this study is to provide evidence on the aphrodisiac property of Eurycoma longifolia Jack. An electric grid was used as an obstruction in the electrical copulation cage in order to determine how much an aversive stimulus the sexually naive male rat for both the treated with E. longifolia Jack and control groups were willing to overcome to reach the estrous receptive female in the goal cage. The intensity of the grid current was maintained at 0.12 mA and this was the intensity in which the male rats in the control group failed to crossover to reach the goal cage. Results showed that E. longifolia Jack continued to enhance and also maintain a high level of both the total number of successful crossovers, mountings, intromissions and ejaculations during the 9-12th week observation period. In conclusion, these results further enhanced and strengthened the aphrodisiac property of E. longifolia Jack.
Angiotensin II is known to act primarily on the angiotensin AT(1) receptors to mediate its physiological and pathological actions. Des-aspartate-angiotensin I (DAA-I) is a bioactive angiotensin peptide and have been shown to have contrasting vascular actions to angiotensin II. Previous work in this laboratory has demonstrated an overwhelming vasodepressor modulation on angiotensin II-induced vasoconstriction by DAA-I. The present study investigated the involvement of the AT(1) receptor in the actions of DAA-I on angiotensin II-induced vascular actions in the renal vasculature of normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and streptozotocin (STZ)-induced diabetic rats. The findings revealed that the angiotensin receptor in rat kidney homogenate was mainly of the AT(1) subtype. The AT(1) receptor density was significantly higher in the kidney of the SHR. The increase in AT(1) receptor density was also confirmed by RT-PCR and Western blot analysis. In contrast, AT(1) receptor density was significantly reduced in the kidney of the streptozotocin-induced diabetic rat. Perfusion with 10(-9)M DAA-I reduced the AT(1) receptor density in the kidneys of WKY and SHR rats suggesting that the previously observed vasodepressor modulation of the nonapeptide could be due to down-regulation or internalization of AT(1) receptors. RT-PCR and Western blot analysis showed no significant changes in the content of AT(1) receptor mRNA and protein. This supports the suggestion that DAA-I causes internalization of AT(1) receptors. In the streptozotocin-induced diabetic rat, no significant changes in renal AT(1) receptor density and expression were seen when its kidneys were similarly perfused with DAA-I.
Angiotensin 1-7, a heptapeptide derived from metabolism of either angiotensin I or angiotensin II, is a biologically active peptide of the renin-angiotensin system. The present study investigated the effect of angiotensin 1-7 on the vasopressor action of angiotensin II in the renal and mesenteric vasculature of Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and streptozotocin-induced diabetic rats. Angiotensin II-induced dose-dependent vasoconstrictions in the renal vasculature. The pressor response was enhanced in the SHR and reduced in the streptozotocin-diabetic rat compared to WKY rats. Angiotensin 1-7 attenuated the angiotensin II pressor responses in the renal vasculature of WKY and SHR rats. However, the ability to reduce angiotensin II response was diminished in diabetic-induced rat kidneys. The effect of angiotensin 1-7 was not inhibited by 1-[(4-(Dimethylamino)-3-methylphenyl] methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate (PD123319), an angiotensin AT(2) receptor antagonist. (D-ALA(7))-Angiotensin I/II (1-7) (D-ALA) (an angiotensin 1-7 receptor antagonist), indomethacin (a cyclo-oxygenase inhibitor), and N(omega)-Nitro-L-Arginine Methyl Ester (L-NAME)(a nitric oxide synthetase inhibitor) abolished the attenuation by angiotensin 1-7 in both WKY rats and SHR, indicating that its action is mediated by angiotensin 1-7 receptor that is either coupled to the release of prostaglandins and/or nitric oxide. The vasopressor responses to angiotensin II in mesenteric vasculature bed was also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses to angiotensin II were relatively smaller in SHR but no significant difference was observed between WKY and streptozotocin-induced diabetic rats. Angiotensin 1-7 attenuated the angiotensin II pressor responses in WKY, SHR and diabetic-induced mesenteric bed. The attenuation was observed at the lower concentrations of angiotensin II in WKY and diabetic-induced rats but at higher concentrations in SHR. Similar observation as in the renal vasculature was seen with PD123319, D-ALA, and L-NAME. Indomethacin reversed the attenuation by angiotensin 1-7 only in the SHR mesenteric vascular bed. The present findings support the regulatory role of angiotensin 1-7 in the renal and mesenteric vasculature, which is differentially altered in hypertension and diabetes.
The present study investigated the action of des-aspartate-angiotensin I (DAA-I) on the pressor action of angiotensin II in the renal and mesenteric vasculature of WKY, SHR and streptozotocin (STZ)-induced diabetic rats. Angiotensin II-induced a dose-dependent pressor response in the renal vasculature. Compared to the WKY, the pressor response was enhanced in the SHR and reduced in the STZ-induced diabetic rat. DAA-I attenuated the angiotensin II pressor action in renal vasculature of WKY and SHR. The attenuation was observed for DAA-I concentration as low as 10(-18) M and was more prominent in SHR. However, the ability of DAA-I to reduce angiotensin II response was lost in the STZ-induced diabetic kidney. Instead, enhancement of angiotensin II pressor response was seen at the lower doses of the octapeptide. The effect of DAA-I was not inhibited by PD123319, an AT2 receptor antagonist, and indomethacin, a cyclo-oxygenase inhibitor in both WKY and SHR, indicating that its action was not mediated by angiotensin AT2 receptor and prostaglandins. The pressor responses to angiotensin II in mesenteric vascular bed were also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses were significantly smaller in SHR but no significant difference was observed between STZ-induced diabetic and WKY rat. Similarly, PD123319 and indomethacin had no effect on the action of DAA-I. The findings reiterate a regulatory role for DAA-I in vascular bed of the kidney and mesentery. By being active at circulating level, DAA-I subserves a physiological role. This function appears to be present in animals with diseased state of hypertension and diabetes. It is likely that DAA-I functions are modified to accommodate the ongoing vascular remodeling.
An earlier study showed that des-aspartate-angiotensin I (DAA-I) attenuated the pressor action of angiotensin III in aortic rings of the spontaneously hypertensive rat (SHR) but not the normotensive Wistar Kyoto (WKY) rat. The present study investigated similar properties of DAA-I in isolated perfused kidneys and mesenteric beds of WKY and SHR. In the renal vasculature, angiotensin III induced a dose-dependent pressor response, which was more marked in the SHR than WKY in terms of significant greater magnitude of response and lower threshold. DAA-I attenuated the pressor action of angiotensin III in both the WKY and SHR. The attenuation in SHR was much more marked, occurring at doses as low as 10(-15) M DAA-I, while effective attenuation was only seen with 10(-9) M in WKY. The effects of DAA-I was not inhibited by PD123319 and indomethacin, indicating that its action was not mediated by angiotensin AT2 receptors and prostaglandins. However, the direct pressor action of angiotensin III in the SHR but not the WKY was attenuated by indomethacin suggesting that this notable difference could be due to known decreased response of renal vasculature to vasodilator prostaglandins in the SHR. Pressor responses to angiotensin III in the mesenteric vascular bed was also dose dependent, but smaller in magnitude compared to the renal response. The responses in the SHR, though generally smaller, were not significantly different from those of the WKY. This trend is in line with the similar observations with angiotensin III and II by other investigators. In terms of the effect of DAA-I, indomethacin and PD123319 on angiotensin III action, similar patterns to those of the renal vasculature were observed. This reaffirms that in the perfused kidney and mesenteric bed, where the majority of the vessels are contractile, femtomolar concentrations of DAA-I attenuates the pressor action of angiotensin III. The attenuation is not indomethacin sensitive and does not involve the angiotensin AT2 receptor. The findings suggest that DAA-I possesses protective vascular actions and is involved in the pathophysiology of hypertension.