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Objectives: Doxorubicin (DOX) is a highly effective antibiotics anthracycline cytotoxic agent with a broad spectrum of activity in the treatment of solid and hematological malignancies. However, DOX is notorious for inducing cardiotoxicity and vascular dysfunction as its common off-target side effects. This study evaluated the possible vasorelaxant activity and mechanism(s) of action of Clerodendrum volubile ethanol leaf extract (CVE) in normal and DOX-pretreated endothelium intact aortic rings in Physiological Salt Solution (PSS) in vitro. Methods: The responses were recorded isometrically by an organ bath connected to Data Capsule Acquisition System. Effects of CVE on phenylephrine-precontracted endothelium intact rat aortic rings and the influence of the respective blockers for adrenergic, cholinergic, calcium channel, and prostacyclin receptors were investigated to unveil the possible underlying vasorelaxant mechanism(s) of CVE. Results: Our findings showed that CVE significantly induced vasorelaxation in phenylephrine hydrochloride (PE) and KCl precontracted endothelium intact aortic rings in a concentration-dependent manner. Furthermore, the CVE-induced vasorelaxation in PE- and KCl-precontracted aortic rings were inhibited by pre-incubation with atropine and indomethacin indicating that the vasorelaxant effect of CVE was profoundly mediated through cholinergic and prostacyclin mechanisms. Conclusion: Overall, results of this study report for the first time the vasorelaxant effect of CVE in isolated endothelium-intact doxorubicin-treated aortic rings of normotensive rats which was probably cholinergic and prostacyclin-mediated. Thus, results of this study provide further insight into the cardioprotective mechanism of CVE in doxorubicin-induced cardiotoxicity beyond the antioxidant and anti-apoptosis mechanisms that have been previously reported.

Introduction Carpolobia lutea root extract (CLRE) has been reported to enhance penile erection. However, the mechanism involved is poorly understood. We investigated in vitro mechanisms of CLRE action on contractile activity of rabbit corpus cavernosum (CC). Methods Corpus cavernosum strips from four healthy male New Zealand rabbits (2.5–3.0 kg) were mounted on an organ chamber and contracted with phenylephrine (PE) (10−9 to 10−5 M) and Potassium Chloride (KCl) (10–50 mM) before treatment with various concentrations of CLRE (0.1–1.2 mg/ml). Interactions between CLRE and a Nitric Oxide Synthase (NOS) inhibitor (N-nitro- l -arginine methyl ester – l -NAME 10−4 M); guanylyl cyclase inhibitors (Oxalodiazolo 4,3-a quinoxalin-1-one – ODQ 10 μM, 20 μM, 30 μM), and (methylene blue 10–30 μM); a cyclooxygenase inhibitor (10−4 M indomethacin); potassium-channel inhibitors (100 μM tetraethyl ammonium TEA), (100 ηM apamin) and (glibenclamide 10 μM and 20 μM); and a calcium-channel inhibitor (−10−4 M nifedipine) were investigated. Results Maximal contractions of KCl and PE contracted CC strips were significantly reduced in a concentration-dependent manner (40.8 ± 3.6% and 38.6 ± 4.0% from 64.6 ± 2.9% and 98.1 ± 4.2% respectively). Relaxant effect of CLRE was significantly reduced by ODQ (38.6 ± 4.0% to 6.4 ± 1.3% and 38.6 ± 4.0% to 7.2 ± 1.2%), nifedipine (38.6 ± 4.0% to 21.1 ± 2.7%) and glibenclamide (40.8 ± 3.6% to 31.5 ± 3.3%). However l -NAME, indomethacin, methylene blue, TEA and apamin did not inhibit relaxation by CLRE. Conclusion Concentration-dependent relaxant effect of CLRE in rabbit CC involves the soluble guanylate cyclase/cyclase Guanosine Monophosphate system, and activation of ATP-dependent K+ channels.

Introduction: Aqueous leave extract of Tridax procumbens (AETPL) is reported to improve erectile functions; however, the mechanism is unclear. This study investigates the mechanism involved in the contractile activity of the corpus cavernosum after AETPL treatment of paroxetine-induced erectile dysfunctional adult male Wistar rats. Methods: A total of 20 male Wistar rats were categorized into four groups of five and treated orally for four weeks: Group 1 (distilled water), Group 2 (paroxetine 10 mg/kg), Group 3 (paroxetine + AETPL 100 mg/kg), and Group 4 (paroxetine + Viagra 0.5 mg/kg). Contractile responses of excised corpus cavernosum strips (CS) were determined in response to acetylcholine (ACh), phenylephrine (PHE), potassium chloride (KCl), and calcium chloride (CaCl2), and after incubation in L-NAME, indomethacin, nifedipine, adenosine, caffeine, nicorandil, and acetovanillone. Results: The relaxation response (%) of CS to ACh was significantly inhibited in the paroxetine group compared to the AETPL- and the Viagra-co-treated group. Pre-incubation in L-NAME considerably enhanced the percentage relaxation in groups co-treated with AETPL and Viagra. Groups co-treated with AETPL and Viagra significantly inhibited contraction in response to cumulative doses of CaCl2. Contractile responses of CS to cumulative doses of PHE after incubation in caffeine and adenosine were considerably inhibited in groups co-treated with AETPL and Viagra. Similarly, nicorandil (10-4 M) enhanced the percentage relaxation to cumulative doses of ACh (10-9 — 10-5 M) in groups co-treated with AETPL and Viagra. The pre-incubation of CS with acetovanillone (10-4 M) enhanced the percentage relaxation to ACh across groups. Conclusion: Erectile dysfunction was reversed by AETPL-induced antioxidant/NADPH oxidase inhibitor activity, reduced calcium sensitivity, activation of ATP-sensitive K+ channel, and endothelial Nitric Oxide (NO) release.

Background. In this study, the male fertility-enhancing activity of 100, 200, and 400 mg/kg/day of Hunteria umbellata water seed extract (HU) in Wistar rats was studied for 60 days. In doing this, effect of repeated doses of HU was studied on the weight gain pattern, gonadosomatic index (GSI), serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TS), prolactin (PRL), and estradiol (ES)} as well as testicular antioxidant status of the treated rats as a way of elucidating the mechanism(s) of action of HU. Method. Thirty-six (36) male Wistar rats were randomly divided into six groups (I-VI) of six rats per group. Group I rats were gavaged with 10 ml/kg/day of distilled water and served as an untreated control; Group II rats were gavaged with 0.3 mg/kg/day of clomiphene in distilled water; Groups III-V rats received 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day of HU, respectively, and Group VI rats received 20 mg/kg/day of Vitamin C all in distilled water. All treatments were for 60 days after which the treated rats were humanely sacrificed. Sera of blood samples were processed for the above stated hormonal profile. Similarly, testicular tissues obtained were processed for semen analysis and complete antioxidant profile of the HU-treated testicles by assaying for superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), glutathione reductase (GSR), glutathione peroxidase (GSH-Px), and Thiobarbituric Reactive Species (TBARS). Results. Prolonged treatments with 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day of HU for 60 days induced dose dependent reductions in weight gain pattern with the most significant (p HU. Conversely, significant (p HU dose. Clomiphene and HU also induced significant (p HU induced profound (p Conclusion. Overall, prolonged oral treatment with 100-400 mg/kg body weight of HU for 60 days significantly improved sperm function which was mediated via enhanced spermatogenesis, steroidogenesis, and antioxidant mechanisms.

Aqueous leaf extract ofTwelve male Wistar rats divided into 2 groups and were treated with either 100 mg/kg of ALETP (ALETP treatment group) or vehicle (distilled water; control group) through oral gavage for 4 weeks. Dose responses of TSM from the 2 groups to acetylcholine (10Treatment with ALETP substantially inhibited TSM contraction stimulated by cumulative doses of acetylcholine, phenylephrine, and KCl. Furthermore, preincubation of TSM from the 2 groups in atropine significantly inhibited contractility in TSM. Incubation in L-NAME and indomethacin also significantly inhibited contractility in TSM of ALETP-treated rats compared to that of controls. Contractile activity of the TSM was also inhibited significantly with incubation in nifedipine in ALETP-treated rats.ALETP enhanced relaxant activity in rat TSM primarily by blocking the L-type calcium channel and promoting endothelial nitric oxide release. ALETP contains agents that may be useful in disorders of the respiratory tract.

Objectives Stress responses vary throughout pregnancy and impact of late gestational variable stress (LGVS) with vitamin C supplementation on uterine contractility is barely explored. This study investigates fetal weight outcome and in-vitro uterine contractile responses to pharmacological agents during LGVS exposure. Methods Twenty four nulliparous pregnant rats were divided into four groups of six. During gestation days 10–19, groups 1 & 2 received normal saline and vitamin C (10 mg/kg) respectively. Groups 3 and 4 were exposed to stress (sleep deprivation, predator exposure, immobility, rapid cage changes, noise, and foreign object) with group 4 concurrently supplemented with vitamin C (10 mg/kg). Serum cortisol, oxidative bio-markers, fetal weights and in-vitro contractile responses of excised uterine tissue to acetylcholine (Ach), oxytocin, calcium chloride (CaCl2), potassium chloride (KCl), diclofenac, and magnesium ions were determined. Results Malondialdehyde activity and cortisol were significantly increased in variable stress only exposed group when compared with control and vitamin C supplemented groups. Fetal body weights, superoxide dismutase and catalase activity were significantly reduced in variable stress only exposed group. Significantly impaired contractile responses to Ach, CaCl2 & KCl in variable stress only exposed group were modulated in vitamin C supplemented groups. Impaired contractile response to oxytocin was however not reversed. Relaxation responses to diclofenac and magnesium ions were statistically unaltered across groups. Conclusions Impaired fetal weights and uterine contractile activity to Ach, CaCl2 and KCl during LGVS was modulated by vitamin C supplementation. Impaired oxytocin contractile activity was however unreversed.

Objective This study investigated the effects of aqueous leaf extract of Tridax procumbens (ALETP) on contractile activity of corpus cavernosum in N-nitro- l -arginine methyl ester ( l -NAME)-induced hypertensive male rats. Methods Twenty normal, adult male rats (130–150 g) were divided into four groups of five rats each. Group I (control) was given normal saline (0.6 mL/kg) and group II was given l -NAME (40 mg/kg) for 6 weeks. Groups III and IV also received l -NAME (40 mg/kg) for 6 weeks but were further co-treated with 100 and 200 mg/kg of ALETP, respectively, from week 4 to week 6. All treatments were given orally. Strips of corpus cavernosum from each of the four groups were exposed to increasing concentrations of acetylcholine (ACh) and sodium nitroprusside (SNP) (10−9–10−5 mol/L) after contraction with phenylephrine (10−7 mol/L) to test for a dose–response effect. Response to potassium and calcium was also measured after cumulatively adding potassium and calcium (10–50 mmol/L) to potassium- and calcium-free organ chamber. Isometric contractions were recorded through an Ugo Basile data capsule acquisition system. Results Mean arterial blood pressure was significantly reduced in the ALETP co-treated group compared to the control and l -NAME-only groups (P l -NAME-only treated group (P Conclusion ALETP treatment of l -NAME-induced hypertensive rats promotes a relaxant effect on isolated cavernosa strips. ALETP shows potential in correcting erectile dysfunction in hypertension.

Objective In this study, we investigated effect of Tridax procumbens aqueous leaf extract (TPALE) on reproductive function in N nitro- l -arginine-methyl ester (L-NAME) induced hypertensive rats. Methodology Twenty healthy, adult male rats (150–190 g) were divided into four groups of five. Group 1 (control) received normal saline (0.6 ml/kg of 0.9% NaCl) orally; groups 2, 3 and 4 received L-NAME (40 mg/kg) orally to induce hypertension for a period of three weeks. Treatments were continued for another 3 weeks with groups 3 and 4 being further treated orally with 100 and 200 mg/kg of TPALE respectively. Blood pressure, body and reproductive organs weight, histology of reproductive organs, fertility success, plasma testosterone and luteinizing hormone (LH) and seminal analysis were determined. Results TPALE decreased systolic, diastolic and mean arterial blood pressure in L-NAME + 100/200 mg/kg TPALE treated groups when compared to L-NAME (40 mg/kg) group. Relative prostate and seminal vesicle weight were significantly reduced in L-NAME group. Motility, viability and count were reduced in L-NAME group when compared to control and TPALE treated group. Fertility success was 100% in all groups except for L-NAME group (0%) with no significant differences in average litter size and weight. Testosterone level increased significantly in TPALE treated group. There was mild interstitial congestion of the epididymis in L-NAME treated groups; tubular diameter also appeared reduced with heightened epithelium for TPALE treated groups. No visible lesions were seen in the testis of all treated groups. Conclusion TPALE exhibits pharmacotherapeutic and protective role on hypertension and reproductive functions in L-NAME induced hypertensive male rats.

Background: Tridax procumbens leaf extract has been reported to show antihypertensive actions through its vasodilatory effects. Although several mechanisms of action have been reported, the sub-cellular mechanism of action of the extract is yet to be fully elucidated. Aim and Objectives: In this study, we investigate the involvement of Na+ - K+ -pump and Na+- Ca2+ exchanger in the vasorelaxant activities of T. procumbens extract (TPE) in isolated rat superior mesenteric arteries. Materials and Methods: Superior mesenteric artery isolated from healthy, young adult Wistar rats (250–300 g) and pre-contracted with phenylephrine (PE) (10-7M) were treated with various concentrations of aqueous extract of TPE (0.5–9 mg/mL). The changes in arterial tension were recorded and interaction between TPE with the selective blocker of Na+ - K+ ATPase (ouabain) and putative Na+-Ca2+ exchanger inhibitor (NiCl2) was evaluated. Results: The result indicated that TPE significantly inhibit the cumulative concentration response curves to PE (10-9 - 10-5 M) in a concentration-dependent manner. Pre-treatment with both ouabain and nickel chloride (NiCl2), abolished the vasorelaxant responses of TPE. Furthermore, TPE reduced the relaxant effect with decreased extracellular Na+ concentration. TPE-induced vasorelaxation was completely abolished in a Na+ -free solution, a condition that eliminates the influence of the forward mode of the exchanger. Conclusion: The results provide direct hypothetical evidence that the activation of Na+ - K+ ATPase and stimulation of the forward mode of the Na+-Ca2+ exchanger contribute to the vasorelaxation induced by TPE in mesenteric artery.

Tridax procumbens is commonly used in traditional medicine in southern part of Nigeria for the treatment of hypertension. However, the mechanism of its antihypertensive properties remains unclear. Attempts were made to investigate the properties of direct actions of aqueous extract of the leaves of T. procumbens on mechanical responses of smooth muscles in aortic ring preparations isolated from the rat. Endothelium-intact aortic rings, isolated from the normotensive rats, had been pre-contracted with noradrenaline, and cumulative addition of the aqueous extract (0.15-1.05 mg/mL) to the bathing fluid induced a concentration-dependent relaxation. Aqueous extract of T. procumbens also attenuated the contractile responses to KCl and shifted the concentration-response curve to the right. The contractile responses to serotonin were also attenuated and the concentration-response curve was shifted to the right in the presence of the extract. The results of this study indicated that aqueous leaf extract of T. procumbens possesses vasodilatory effects on the aortic smooth muscles isolated from the rat. Based on these results, a possible mechanism involved in the relaxing actions of the extract on vascular smooth muscle was discussed. The results of this study may provide a scientific basis for the use of this extract to the treatment of hypertension in Nigerian traditional medicine.

BACKGROUND The effect of Tridax procumbens aqueous ethanolic extract on the rat corpus cavernosum smooth muscles was evaluated in the present study. METHOD Corpus cavernosum strips obtained from healthy, young, adult male Wistar albino rats (250-300 g) were precontracted with phenylephrine (10-7 M) or KCl (60 mM) and then treated with various concentrations of T. procumbens extract (0.15-1.05 mg/mL). The change in corpus cavernosum strip tension was recorded. The interactions between T. procumbens extract with acetylcholine and with sodium nitroprusside were also evaluated. RESULTS The results indicated that corpus cavernosum strips relaxation induced by T. procumbens extract was concentration-dependent and this was significant (p

BACKGROUND Tridax procumbens leaf extract has a folk reputation as an antihypertensive agent in Nigeria. Evidence suggests that it has a relaxant effect on smooth muscles. The present study was designed to investigate the role of calcium in the vasorelaxant effect of this extract. METHODS Concentration-response studies with noradrenaline (NA), KCl and CaCl2 were carried out in rat aortic rings with and without the extract in physiological salt solution (PSS) (n=6 each). Also, the role of intracellular calcium mobilization was studied by measuring the phasic response to NA in Ca2+-free N,N-ethylene glycol tetraacetic acid (EGTA) PSS (n=6). RESULTS The results showed that the contractile responses to either NA or KCl were attenuated (p

Background: Cardiovascular disease is a widespread public health problem and hypertension is one of the major risk factor. Tridax procumbens leaf extract is traditionally used in the treatment of hypertension. This study evaluate the effects of Tridax procumbens extract (TPE) on blood biochemical parameters of N-nitro-L-arginine methyl ester (L-NAME) induced hypertensive rats. Materials and Methods: Rats were divided randomly into four different treatment groups. Group I received 0.9 % NaCl (Control), Group II, III and IV were given a NOS inhibitor (L-NAME) 40 mg/kg/day, orally for 6 weeks to induce hypertension. Groups III and IV were further treated with TPE (100 and 200 mg/kg/day) respectively in the last 3 weeks of 6 weeks. Blood pressure, morphological variables, histopathology, plasma lipids, lipoproteins and cholesterol levels, hepatic enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and other parameters were analyzed. Results TPE markedly inhibited the sustenance of L-NAME-induced hypertension. This effect was accompanied by a partial or full amelioration of most of the adverse effects induced by L-NAME, such as: (1) increases in blood pressure, organs weight indices; (2) hyperlipidemia; (3) increased plasma activity of glutamic-pyruvic transaminase (ALT) and AST (4) liver and cardiac histological lesions. Conclusions This study provides evidence about the antihypertensive effects and end-organ protection of Tridax procumbens extract in animal model of hypertension. These effects may be due to one or more constitution in this extract

Background/Aim: Tridax procumbens (Linn) (Asteraceae) is one of the herbs widely distributed in many parts of the world. Its leaves have long been used for the treatment of hypertension in Nigeria. Previous studies have shown that aqueous leaves of T. procumbens extract (TPE) lowers blood pressure through endothelium-dependent and -independent mechanism in the aortic rings isolated from normotensive rats. The aim of the present study was to further investigate mechanisms of TPE-induced relaxation in the aortic artery by assessing its mechanistic interactions with nitric oxide (NO) synthase, cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP). Materials and Methods: The aortic artery isolated from healthy, young adult normotensive Wistar albino rats (250-300 g) were pre-contracted with phenylephrine (PE) (10–7 M) and KCl (60 mM) and were treated with various concentrations of aqueous extract of TPE (0.5-9.0 mg/ml). The changes in arterial tension were recorded using Ugo Basile model 7004 coupled to data capsule acquisition system model 17400. The interaction between TPE with cAMP and cGMP inhibitors was also evaluated. Results: The results showed that the TPE (0.5-9.0 mg/ml) significantly (P < 0.05) reduced the contraction induced by PE in a concentration-dependent manner. The vasorelaxant effect caused by the TPE was significantly (P < 0.05) attenuated with pre-incubation of cGMP (Rp-8Br PET cGMPS) and cAMP (Rp-AMP) inhibitor, respectively. Conclusion: These results suggest that TPE causes vasodilatory effects in a concentration-dependent manner in the isolated rat aortic artery. The mechanism of action of TPE is complex. A part of its relaxing effect is mediated directly by blocking or modulating cGMP and cAMP.