Cardiovascular effects of (13S)-9_, 13_- epoxylabda-6_(19), 15(14)diol dilactone, a diterpenoid isolated from the organic extract of leonotis leonurus leaves, in anaesthetized normotensive rats

Philosophiae Doctor - PhDPlants used in traditional medicines have served as sources of some of the drug compounds used in medicines today, and could still serve as leads for then development of new drugs to treat existing chronic diseases such as hypertension. This study was aimed at the isolation and identification of a cardio-active compound from L. leonurus, a plant commonly used in traditional medicines in South Africa for the treatment of hypertension and other cardiac problems. The possible mechanisms by which the isolated compound produced its effect on the cardiovascular system were explored using the anaesthetized normotensive rat model.Fractionation of the organic extracts of the leaves led to the isolation of a novel diterpene,(13S)-9 , 13 -epoxylabda-6 (19),15(14)diol dilactone (EDD) whose structure was elucidated using infra red (IR), nuclear magnetic resonance (NMR), mass spectroscopy(MS), and X-ray diffraction analysis. In anaesthetized normotensive male Wistar rats, EDD(0.5 mg/kg – 5.0 mg/kg; IV) produced slight non-significant decreases in systolic pressure(SP), diastolic pressure (DP), and mean arterial pressure (MAP) with the lower (0.5 mg/kg– 2.0 mg/kg) doses, while significant increases in SP, DP and MAP occurred with the higher (3.0 mg/kg – 5.0 mg/kg) doses. All doses of EDD administered also produced significant decreases in heart rate (HR).Prazosin and reserpine pre-treatment abolished the vasoconstrictive effect of EDD,suggesting an indirect vasoconstrictive effect for EDD via the release of catecholamines.Atenolol pre-treatment led to increases in the negative chronotropic effect of EDD, while the positive chronotropic effect of dobutamine was significantly decreased by EDD,suggesting the involvement of the 1 adrenoceptor in the negative chronotropic effect of EDD. In animals pre-treated with verapamil, a cardio-selective Ca2+ channel blocker, no significant changes in HR occurred with all EDD doses, but HR values were significantly lower than those obtained with EDD in non pre-treated animals.The results of this study indicate that (13S)-9 , 13 -epoxylabda-6 (19),15(14)diol dilactone, a novel dilactone diterpene isolated from the leaves of L. leonurus has an effect on the cardiovascular system. EDD exhibits a dual effect on the cardiovascular system by producing a vasoconstrictive effect accompanied by bradycardia. The vasoconstrictive effect of EDD is probably due to the release of catecholamines, while the negative chronotropic effect is probably due to 1 adrenoceptor antagonism. Further studies are however required to fully determine the mechanism by which EDD produces its cardiovascular effects

Comparison of the acute effects of Tulbaghia violacea William Henry Harvey (Alliaceae) on blood pressure and heart rate of ageing male normotensive Wistar kyoto rats and adult male spontaneously hypertensive rats

Purpose: To assess the effect of the crude methanol leaf extracts of Tulbaghia violacea William Henry Harvey (Alliaceae) on blood pressure (BP) and heart rate in ageing normotensive Wistar Kyoto rats (WKY), and compare the results obtained with those for adult spontaneously hypertensive rats (SHR).Methods: T. violacea (5 – 150 mg/kg) and/or vehicle (dimethylsulfoxide and normal saline) were respectively and randomly administered intravenously to groups of ageing (15 months) WKY and adult (< 5 months) SHR, weighing 380 - 470 and 280 - 320 g, respectively. BP and heart rate (HR) were measured via a pressure transducer connecting the femoral artery and Powerlab equipment.Results: T. violacea significantly and dose-dependently reduced systolic BP, diastolic BP, mean arterial pressure (MAP) and HR in both strains of rats. No statistically significant differences were however observed when the changes in BP and HR in the two rats strains were compared.Conclusion: T. violacea was effective in reducing BP and HR in both age-induced and spontaneously hypertensive rats.Keywords: Age, Wistar Kyoto rats, blood pressure, heart rate, Tulbaghia violace

Potential beneficial effects of Tulbaghia violacea William Henry Harvey (Alliaceae) on cardiovascular system - A review

Tulbaghia violacea William Henry Harvey (Harv. Alliaceae) is a small bulbous herb belonging to the family Alliaceae. It is used in South Africa to treat fever, colds, asthma, paralysis, and hypertension. Meanwhile, cardiovascular disease accounts for about 30 % of total global death, with most of these deaths occurring in low and middle-income countries. Furthermore, people in low-income countries are still largely dependent on plants in their surroundings for both prophylaxis and treatment of diseases, partly due to limited access to and cost of pharmaceuticals, and folkloric evidence of the potency of medicinal plants and/or local belief systems. Therefore, the present review aims to proffer possible ways by which T. violacea may improve cardiovascular outcomes. An extensive and systematic review of the literature was carried out, and relevant findings presented in this review. There is evidence that T. violacea may modulate the renin-angiotensin system, the autonomic nervous system, oxidative stress and haemostasis, with resultant protection of the cardiovascular system in both health and disease.Web of Scienc

Service learning in pharmacy: Opportunities for student learning and service delivery

High patient load and understaffing in public health care facilities preclude the provision of optimal pharmaceutical services in South Africa. A Service Learning in Pharmacy (SLIP) programme for the University of the Western Cape's final year pharmacy students was implemented in health care facilities to assist in service provision. Students rotated between a pharmacotherapy (patient-oriented) and pharmaceutical formulation (product-oriented) activities to develop skills in prescription analysis, manufacturing and packaging of hospital pharmaceuticals. Structured focus group sessions were held with students and pharmacists to assess the integrated service learning experiences. Student feedback was positive, as the 'real world' experiences enabled them to adapt to intense work pressures, developed a sense of 'personal responsibility' towards patient health and they were sensitized to issues of social injustice. Students became competent in prescription analyses, counseling on medication use, manufacturing and pre-packing procedures. Pharmacists fully supported increased student involvement in the health services. Service learning in pharmacy schools is needed to contextualize learning and to address health care needs in South Africa

Pulmonary effects and disposition of luteolin and Artemisia afra extracts in isolated perfused lungs

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia afra (Asteraceae) is a traditional medicinal plant frequently used in steam inhalation form to treat respiratory conditions. AIM OF THE STUDY: Quantify luteolin content in Artemisia afra dried crude and aqueous extract. Evaluate the pulmonary effects of Artemisia afra steam inhalation, nebulized Artemisia afra extract and luteolin in isolated perfused lungs (IPL). Evaluate the pulmonary disposition of intravenously administered luteolin. MATERIALS AND METHODS: HPLC was used to quantify luteolin in Artemisia afra extracts. A modified version of the IPL was used to determine the effects of Artemisia afra steam inhalation, nebulized luteolin, and nebulized aqueous leaf extract on lung function, as well as the pulmonary disposition of IV luteolin. RESULTS: Artemisia afra extract contained significantly higher luteolin levels than the crude dried leaves. Inhaled Artemisia afra steam, and nebulized luteolin, and Artemisia afra extract and IV luteolin produced significant dose-dependent improvements in lung function, with nebulized Artemisia afra producing the greatest improvements. Nebulisation with Artemisia afra extract yielded higher quantities of luteolin than luteolin nebulisation. CONCLUSION: Results verify the traditional use of inhalation of Artemisia afra steam, although nebulized luteolin and aqueous extract are better alternatives. Luteolin significantly contributes to the broncho-dilatory effects of Artemisia afra.Web of Scienc

Crataegus monogyna and centella asiatica extracts as inhibitors of cathepsin s

Cathepsin cysteine proteases such as cathepsin S are responsible for the unfavorable and irreversible dysregulation of extracellular matrix (ECM) proteolysis found in cardiomyopathy, heart valve diseases and atherosclerosis. Cathepsin S plays a central role in ECM remodeling, which has been implicated in the development and progression of cardiovascular diseases. The current study aimed to evaluate the aqueous and ethanol extracts of the berries of Crataegus monogyna and the leaves of Centella asiatica for inhibition of cathepsin S activity using an in vitro fluorescent assay

In-silico and in-vivo evaluation of the cardiovascular effects of five Leonotis leonurus diterpenes

Leonotis leonurus extracts and compounds have been extensively studied for pharmacological effects. However, most of the diterpenes isolated from the plant have not been evaluated as possible contributors to the cardiovascular effects of the plant extracts. In this study, computational modelling was used to predict the drug-likeness and cardiovascular effects of five diterpenoids of L. Leonurus. The predicted results were then subsequently compared with results obtained from anaesthetized normotensive Wistar rats to determine the most likely lead compounds for drug development. Molecular operating environment (MOE) software was used to assess the drug-likeness and molecular docking interactions between the diterpenoids and the angiotensin-converting enzyme (ACE) (PDB; 2 × 8Z), the angiotensin receptor (AT1) (PDB; 3R8A) and the β1 receptor (PDB; 2Y04). The predicted cardiovascular effects were assessed in the anaesthetized normotensive Wistar rat model

Bioprospecting of Helichrysum species: Chemical profile, phytochemical properties, and antifungal efficacy against botrytis cinerea

Variation in plant species and extraction solvents play a crucial role in the recovery of their bioactive compounds and antifungal efficacy. Thus, in this study, a comparative investigation was carried out using extraction solvents: 70% acetone and 95% ethanol to obtain crude aqueous extracts from Helichrysum odoratissimum and H. patulum. Crude aqueous extracts were screened using gas chromatography–mass spectrometry (GC–MS), to gain insight into their chemical composition. Phytochemical properties (total polyphenols (TP) and radical scavenging capacity via 2,2-diphenyl-1-picrylhydrazyl (DPPH)), and antifungal activity against Botrytis cinerea of the crude extracts were evaluated. Fungicide (Rovral® WP) and extraction solvents were used as controls

Proprotein convertase subtilisin/kexin type 9 genetic screening using the vervet (Chlorocebus aethiops) model

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has come to prominence due to its reported function in the clearance of low-density li-poprotein cholesterol. The vervet monkey (Chlorocebus aethiops) was utilized to study the genetics of PCSK9 gene. Method: Sixteen vervet monkeys were selected to screen for possible PCSK9 poly-morphisms and to determine gene expression. Results: Four PCSK9 sequence variants (T112T, R148S, H177N and G635G) were identified and three of these variants (H177N, R148S, and G635G) were categorized as loss of function mutations. A decline in gene expression levels was also observed in animals harboring these three variants. Although the selected variants might have affected the level of gene expression in the selected animals, individual variation was also noticed in some of these individuals with the G635G variant. Conclusion: Based on the findings obtained from this study, it is suggestive that the activity of PCSK9 was hindere

Pulmonary effects and disposition of luteolin and Artemisia afra extracts in isolated perfused lungs

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia afra (Asteraceae) is a traditional medicinal plant frequently used in steam inhalation form to treat respiratory conditions. AIM OF THE STUDY: Quantify luteolin content in Artemisia afra dried crude and aqueous extract. Evaluate the pulmonary effects of Artemisia afra steam inhalation, nebulized Artemisia afra extract and luteolin in isolated perfused lungs (IPL). Evaluate the pulmonary disposition of intravenously administered luteolin. MATERIALS AND METHODS: HPLC was used to quantify luteolin in Artemisia afra extracts. A modified version of the IPL was used to determine the effects of Artemisia afra steam inhalation, nebulized luteolin, and nebulized aqueous leaf extract on lung function, as well as the pulmonary disposition of IV luteolin. RESULTS: Artemisia afra extract contained significantly higher luteolin levels than the crude dried leaves. Inhaled Artemisia afra steam, and nebulized luteolin, and Artemisia afra extract and IV luteolin produced significant dose-dependent improvements in lung function, with nebulized Artemisia afra producing the greatest improvements. Nebulisation with Artemisia afra extract yielded higher quantities of luteolin than luteolin nebulisation. CONCLUSION: Results verify the traditional use of inhalation of Artemisia afra steam, although nebulized luteolin and aqueous extract are better alternatives. Luteolin significantly contributes to the broncho-dilatory effects of Artemisia afra.Web of Scienc