Moroccan Antihypertensive Plants and their Mechanisms of Action.

BACKGROUND: The use of herbal remedies, medicinal plants, and their derivatives for the treatment and control of hypertension is well-known and widespread throughout Morocco. AIMS: The aim of the study was to review the antihypertensive and vasorelaxant medicinal plants of the Moroccan pharmacopeia. OBJECTIVE: To date, no review on Moroccan medicinal plants exhibiting antihypertensive effects has been performed, and their mechanism of action has not been specified. The objective of this review was to collect, analyze, and critically assess published publications on experimental and clinical research that explored the blood pressure-reducing abilities of Moroccan medicinal plant extracts. MATERIALS AND METHODS: This study collected, processed, and critically analyzed published studies related to experimental and clinical research that investigated Moroccan herbal derivatives' blood pressure-lowering abilities using a number of scientific databases, including ScienceDirect, Scopus, PubMed, Google Scholar, and others. Plantlist.org was used to validate the right plant names. RESULTS: The results revealed 22 species of Moroccan medicinal plants belonging to 13 different groups with recognized antihypertensive properties. The species were abundant in a variety of chemical elements. Asteraceae (08 species), Lamiaceae (3 species), Apiaceae (2 species), and 1 species each from the following families: Parmeliaceae, Fabaceae, Cistaceae, Malvaceae, Polygonaceae, Brassicaceae, Myrtaceae, Rutaceae, Amaranthaceae, Rosaceae, and Lauraceae were the most frequently mentioned families for their antihypertensive properties. The most used parts were the leaves and the aerial parts. The two main methods of preparation among Moroccans were decoction and infusion. This study demonstrated the known antihypertensive and vasorelaxant properties of Moroccan medicinal plants in vivo and in vitro, as well as their mechanisms of action. Interestingly, phytochemicals can operate on blood vessels directly via a vasorelaxant impact involving a range of signaling cascades or indirectly by blocking or activating multiple systems, such as an angiotensin-converting enzyme (ACE), renin-angiotensin system (RAS), or diuretic activity. CONCLUSION: The review of the available data reveals that more work needs to be done to examine all the Moroccan medicinal plants that have been suggested as antihypertensive in published ethnopharmacological surveys. A review of the literature in this area reveals that methodologies of the experimental study need to be standardized, and purified molecules need to be studied. In addition, mechanistic investigations, when they exist, are generally incomplete. In contrast, only a few advanced clinical investigations have been conducted. However, all studies fail to determine the efficacy/safety ratio.

The effect of purple-black barberry (Berberis integerrima) on blood pressure in subjects with cardiovascular risk factors: a randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberis integerrima commonly known as "barberry" belongs to the Berberidaceae family and has been used as a medicinal plant in Iranian traditional medicine. AIM OF THE STUDY: Our aim in this study was to investigate the effects of barberry consumption on blood pressure (BP). MATERIALS AND METHODS: Eighty-four medicated hypertensive patients were selected and randomly allocated to barberry and placebo groups. The barberry group received 10 g/day dried purple-black barberry powder, once daily, for 2-months. Systolic, diastolic, and mean arterial BP was assessed through 24-h ambulatory BP monitoring before and after 2-month treatment. The estimation of sodium and potassium intake was done through measurement of sodium and potassium in 24-h urinary samples. Plasma and urinary nitrite, and nitrate (NOx) levels, as well as plasma angiotensin-converting enzyme (ACE) activity, were also determined. RESULTS: Seventy-eight participants with an average age of 54.12 ± 10.32 years and BMI of 27.93 ± 2.22 kg/m2 completed the study. There was no significant difference in body weight, physical activity, and the 24-h urinary sodium and potassium excretion between the two groups before and after the study. After adjusting for baseline values and changes in sodium intake, systolic, and mean arterial BP decreased significantly in the barberry group compared to the placebo group (p = 0.015 and p = 0.008, respectively). Plasma NOx levels and ACE activity were not different between the two groups, but urinary NOx was increased significantly in the barberry group compared to the placebo group (p = 0.008). CONCLUSIONS: In patients treated with antihypertensive drugs, daily consumption of purple-black barberry can be effective in improving systolic BP control.

Pharmacological basis for the antihypertensive activity of Grewia asiatica fruit extract.

In the management of cardiovascular disorders, medicines from herbal sources have played a vital role through centuries. The following study was commenced in order to lay possible pharmacological foundation associated with medicinal uses of edible fruit of Grewia asiatica in hypertension through in-vitro method. In this study isolated atrial preparation of Guinea pig was used where crude ethanolic extract of Grewia asiatica fruit (Ga.Cr) decreased the force and rate of spontaneous atrial contractions (0.03-10mg/kg). In isolated rat aortic ring preparations previously vasoconstricted by phenylephrine and High K+, it also resulted in dose dependent vasodilation (0.01-10 mg/kg).In the presence of L-NAME, the relaxation curve of Ga.Cr was partially inhibited showing involvement of Nitric oxide (NO) mediated pathway. The speculative analysis contemplated that Ga.Cr has blood pressure reducing potentials through inhibition of Ca++ influx via Ca++ channels, its release from intracellular stores and through other means like NO mediated pathways.

Bioactive Compounds From Coptidis Rhizoma Alleviate Pulmonary Arterial Hypertension by Inhibiting Pulmonary Artery Smooth Muscle Cells' Proliferation and Migration.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a devastating disorder characterized by excessive proliferation and vasoconstriction of small pulmonary artery vascular smooth muscle cells (PASMCs). Coptidis rhizoma (CR) because of the complexity of the components, the underlying pharmacological role and mechanism of it on PAH remains unknown. In this article, the network pharmacological analysis was used to screen the main active constituents of CR and the molecular targets that these constituents act on. Then, we evaluated the importance of berberine and quercetin (biologically active components of CR) on the proliferation and migration of PASMCs and vascular remodeling in experimental models of PAH. Our results showed that berberine and quercetin effectively inhibited the proliferation and migration of hypoxia-induced PASMCs in a manner likely to be mediated by the suppression of MAPK1, NADPH oxidase 4 (NOX4), and cytochrome P450 1B1 (CYP1B1) expression. Furthermore, berberine and quercetin treatment attenuates pulmonary hypertension, reduces right ventricular hypertrophy, and improves pulmonary artery remodeling in monocrotaline-induced pulmonary hypertension in rat models. In conclusion, this research demonstrates CR might be a promising treatment option for PAH, and the network pharmacology approach can be an effective tool to reveal the potential mechanisms of Chinese herbal medicine.

Cardioprotective, hypotensive and toxicological studies of Populus ciliata (Wall. ex Royle).

Populus ciliata Wall ex. Royle has folkloric repute to treat various cardiovascular ailments and related disorders. The current study was designed to evaluate the toxic profile, cardioprotective and hypotensive effects of Populus ciliata (Wall. ex Royle). Populus ciliata crude ethanolic extract (Pc. Cr) and its aqueous (Pc. Aq) & organic (Pc. Dcm) fractions were tested on isolated aorta of rat and rabbit having intact and non-intact endothelium respectively. Pc. Cr & Pc. Aq relaxed the contractions induced by PE (1 µM)-induced and K+ (80 mM)-induced on aorta, possibly by mediating endothelium derived relaxing factor (EDRF) in intact endothelium and voltage dependent L-type calcium channels blocking (CCB) mechanism in non-intact endothelium. Pc. Cr showed anti-hypertensive & cardioprotective activity by decreasing force of contraction & heart rate on isolated rabbit paired atria and reduced blood pressure in anesthetized rat. Cardioprotective effect of Pc. Cr was assessed in isoproterenol induced acute myocardial infarction (AMI) and left ventricular hypertrophy (LVH) in Sprague Dawley rats. In LVH, Pc. Cr exerted positive effects by decreasing angiotensin II & renin and increasing cGMP & nitric oxide (NO) with reduced cardiac fibrosis, necrosis and cardiac cell size. In AMI, Pc. Cr responded effectively by decreasing cardiac markers creatinine kinase (CK), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LD) in blood associated with less edema and necrosis. Presence of catechin, vinallic acid, P-coumeric acid and quercitin identified through HPLC support the effectiveness of Pc. Cr in hypertension, AMI and LVH. Pc. Cr showed no significant adverse effects in Sprague Dawley albino rats after acute & sub-acute treatment in histopathological investigation. Extract of Populus ciliata showed vasorelaxant, hypotensive and cardioprotective effect in Sprague Dawley albino rats and white albino rabbit by mediating EDRF and voltage dependent L-type CCB mechanism respectively.

A systematic review with meta-analysis on the antihypertensive efficacy of Nigerian medicinal plants.

ETHNOPHARMACOLOGICAL RELEVANCE: Despite the promising effects of herbal preparations in lowering blood pressure (BP), hypertension remains a major clinical challenge in Nigeria. The BP-lowering effects of medicinal plants are due to the presence of bioactive compounds. AIM OF THE STUDY: This meta-analysis presents a precise estimate of the therapeutic benefits of medicinal plants utilized in Nigeria for the management of hypertension in animals and humans. METHODS: A systematic literature search was performed through Cochrane, PubMed, Science Direct and Scopus databases from inception until February 28, 2021 using search terms related to randomized controlled trials of Nigerian medicinal plants for hypertension. Additional studies were identified through manual search. BP was the main outcome that was measured after the intervention. Meta-analysis was performed using the Review Manager and Meta-Essential. RESULTS: Nineteen trials comprising of 16 preclinical and 3 clinical studies were enrolled for the meta-analysis. A total number of 16 plants was identified of which H. sabdariffa was the highest reported plant. The plant extracts significantly lowered the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the hypertensive subjects compared to control. Weighted mean difference (WMD) for SBP (-43.60 mmHg, 95% CI: -63.18, -24.01; p<0.0001) and DBP (-29.50 mmHg, 95 CI: -43.66, -15.34; p<0.0001) was observed for the preclinical studies. For clinical trials, the WMD was -13.98 mmHg, 95 CI: -19.08, -8.88; p<0.00001 for SBP and -10.00 mmHg, 95 CI: -12.22, -7.78; p<0.00001 for DBP. High heterogeneity was observed for the outcome measures of preclinical studies, but not for the clinical studies. The observed substantial heterogeneity in preclinical studies may be linked to methodological shortcomings as evidenced by the results of the risk of bias assessment. There was no evidence of publication bias in animal trials for BP using the funnel plot and Egger's regression test (SBP, p=0.239 and DBP, p=0.112). CONCLUSIONS: This study provides evidence of medicinal preparations for the treatment of hypertension. A well-conducted trial with methodological rigour and a longer duration of follow-up is required for their effective clinical utilization.

Effects of Chrysophyllum albidum fruit pulp on haemodynamic parameters, pro-inflammatory markers, antioxidant parameters and critical biomolecules associated with hypertension-in vivo.

The effects of Chrysophyllum albidum fruit pulp on haemodynamic parameters, pro-inflammatory markers, antioxidant parameters and critical biomolecules associated with hypertension in vivo were determined. Feeding with supplemented diet with pulp reduced heart rate, mean arterial pressure, systolic and diastolic blood pressure levels of hypertensive-treated groups. Moreover, hypertensive-treated groups fed with fruit pulp supplemented diets had significantly (p < 0.05) lower level of serum pro-inflammatory markers when compared to untreated hypertensive group. Furthermore, feeding with supplemented diet with pulp and captopril administration reduced AChE, BChE, ACE, and arginase activities of hypertensive-treated groups. The fruit pulp supplemented diet also increased antioxidant status of hypertensive-treated groups. This was supported by the histopathological examination of the kidney and heart tissues. These beneficial effects could in part be the explanations of ethnomedicinal uses of the fruit pulp in the management of hypertension. Nevertheless, the higher percentage inclusion of the pulp showed higher antihypertensive effects.

Polyphenolic Composition and in Vitro Antihypertensive and Anti-Inflammatory Effects of Cuphea lindmaniana and Cuphea urbaniana.

The present study investigates the chemical composition, anti-inflammatory, and antihypertensive activities, in vitro, from extracts of Cuphea lindmaniana and Cuphea urbaniana leaves. The extraction was performed ultrasound-assisted, and UHPLC/MS analysis was in positive mode ionization. The anti-inflammatory activity of the extracts and miquelianin were assayed at concentrations 0.001-10 µg/mL by chemotaxis on rat polymorphonuclear neutrophils. The antihypertensive activity was performed by angiotensin-converting enzyme (ACE) inhibition. From the nineteen proposed compounds, six of them are described for the first time in this genus. The extracts displayed antichemotactic effect with a reduction of 100 % of the neutrophil migration, in vitro, in most concentrations. The ACE-inhibition presented results ranging from 19.58 to 22.82 %. In conclusion, C. lindmaniana and C. urbaniana extracts contain a rich diversity of flavonoids and display in vitro anti-inflammatory and antihypertensive potential. Thus, this study could serve as a scientific baseline for further investigation, on developmental novel products with therapeutic actions.

Protease Inhibitors Purified from the Canola Meal Extracts of Two Genetically Diverse Genotypes Exhibit Antidiabetic and Antihypertension Properties.

Valorization of vegetable oil waste residues is gaining importance due to their high protein and polyphenol contents. Protease inhibitors (PIs), proteins from these abundantly available waste residues, have recently gained importance in treating chronic diseases. This research aimed to use canola meal of genetically diverse Brassica napus genotypes, BLN-3347 and Rivette, to identify PIs with diverse functionalities in therapeutic and pharmacological applications. The canola meal PI purification steps involved: native PAGE and trypsin inhibition activity, followed by ammonium sulfate fractionation, anion exchange, gel filtration, and reverse-phase chromatography. The purified PI preparations were characterized using SDS-PAGE, isoelectric focusing (IEF), and N terminal sequencing. SDS-PAGE analysis of PI preparations under native reducing and nonreducing conditions revealed three polymorphic PIs in each genotype. The corresponding IEF of the genotype BLN-3347, exhibited three acidic isoforms with isoelectric points (pI) of 4.6, 4.0, and 3.9, while Rivette possessed three isoforms, exhibiting two basic forms of pI 8.65 and 9.9, and one acidic of pI 6.55. Purified PI preparations from both the genotypes displayed dipeptidyl peptidase-IV (DPP-IV) and angiotensin-converting enzyme (ACE) inhibition activities; the BLN-3347 PI preparation exhibited a strong inhibitory effect with lower IC50 values (DPP-IV 37.42 µg/mL; ACE 129 µg/mL) than that from Rivette (DPP-IV 67.97 µg/mL; ACE 376.2 µg/mL). In addition to potential human therapy, these highly polymorphic PIs, which can inhibit damaging serine proteases secreted by canola plant pathogens, have the potential to be used by canola plant breeders to seek qualitative trait locus (QTLs) linked to genes conferring resistance to canola diseases.

Açaí Reverses Adverse Cardiovascular Remodeling in Renovascular Hypertension: A Comparative Effect With Enalapril.

ABSTRACT: This study aimed to determine if açai seed extract (ASE) could reverse pre-existing cardiovascular and renal injury in an experimental model of renovascular hypertension (2 kidney, 1 clip, 2K1C). Young male rats (Wistar) were used to obtain 2K1C and sham groups. Animals received the vehicle, ASE (200 mg/kg/d), or enalapril (30 mg/kg/d) in drinking water from the third to sixth week after surgery. We evaluated systolic blood pressure by tail plethysmography, vascular reactivity in the rat isolated mesenteric arterial bed (MAB), serum and urinary parameters, plasma inflammatory cytokines by ELISA, MAB expression of endothelial nitric oxide synthase and its active form peNOS by Western blot, plasma and MAB oxidative damage and antioxidant activity by spectrophotometry, and vascular and cardiac structural changes by histological analysis. ASE and enalapril reduced the systolic blood pressure, restored the endothelial and renal functions, and decreased the inflammatory cytokines and the oxidative stress in 2K1C rats. Furthermore, both treatments reduced vascular and cardiac remodeling. ASE substantially reduced cardiovascular remodeling and recovered endothelial dysfunction in 2K1C rats probably through its antihypertensive, antioxidant, and anti-inflammatory actions, supplying a natural resource for the treatment of renovascular hypertension.

Methanol (80%) leaf extract of Otostegia integrifolia Benth (Lamiaceae) lowers blood pressure in rats through interference with calcium conductance.

BACKGROUND: Otostegia integrifolia Benth. (Lamiaceae) leaves are used to treat hypertension in Ethiopian folk medicine. However, the claim has so far not been investigated scientifically. Thus, the objective of this study was to evaluate the antihypertensive activity of 80% methanol leaf extract of O. integrifolia in animal model of hypertension and possible underlying mechanisms in isolated rat aorta. METHODS: Antihypertensive effect of various oral doses of the extract (250, 500 and 1000 mg/kg) was determined in fructose-induced hypertensive rats using the non-invasive tail-cuff method. Thoracic aortic strips of rats were isolated and suspended in organ bath, and the vasodepressor effect as well as the possible mechanism (s) of action were studied by means of isometric tension recording experiments ex vivo. Phytochemical analysis was also performed to suggest possible constituents related to the activity. RESULTS: Blood pressure was significantly lowered in a dose-dependent manner following extract administration, suggesting that the extract possesses antihypertensive activity. The extract also caused a dose-dependent relaxation of aortic strip precontracted with KCl at a concentration of 6.25-125 µg/L, with a maximum relaxation (100%) achieved at a cumulative concentration of 318.75 µg/ml. The relaxation mechanism was found to be independent of muscarinic receptors, prostanoids, histamine receptors, ATP dependent K+ channels, sarcoplasmic reticulum stored Ca2+ and the endothelium system. The extract shifted the Ca2+ concentration-response curve to the right similar to that caused by nifedipine, suggesting that vasorelaxation could possibly be mediated via calcium channel blockade. The extract was found to contain phenolic compounds (164.3 mg/g, expressed as gallic acid equivalents) and flavonoids (125.7 mg/g, expressed as quercetin equivalents). CONCLUSION: The findings revealed that the plant is endowed with antihypertensive activity, providing evidence for its traditional use. The effect maybe, at least in part, due to dilation of blood vessels through blockade of Ca+ 2 channels mediated by phenolic and flavonoid constituents.

Vasorelaxant and Antihypertensive Effects of Mentha pulegium L. in Rats: An In vitro and In vivo Approach.

Aims The aim of the study was to investigate the effect of aqueous aerial part extract of Mentha pulegium L. (Pennyrile) (MPAE) on arterial pressure parameters in rats. BACKGROUND: Mentha pulegium is a medicinal plant used to treat hypertension in the Moroccon population. METHODS: In the current study, MPAE was prepared and its antihypertensive activity was pharmacologically investigated. L-NAME-hypertensive and normotensive rats received MPAE (180 and 300 mg/kg) orally for six hours for acute experiment and during seven days for the sub-chronic treatment. Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. In the in vitro experiment, isolated denuded and intact thoracic aortic rings were suspended in a tissue bath system and the tension changes were recorded. RESULTS: A fall in blood pressure was observed in L-NAME-induced hypertensive treated with MPAE. The extract also produced a dose-dependent relaxation of aorta pre-contracted with NE and KCl. The study showed that the vasorelaxant ability of MPAE seems to be exerted through the blockage of extracellular Ca2+ entry. CONCLUSION: The results demonstrate that the extract of pennyrile exhibits antihypertensive activity. In addition, the effect may be, at least in part, due to the dilation of blood vessels via blockage of Ca2+ channels.

Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolites.

ETHNOPHARMACOLOGICAL RELEVANCE: Tagetes lucida Cav. commonly known as "yauhtli" or "pericón" is used in Mexican traditional medicine for the treatment of anxiety, depressant diseases, pain, hypertension, among others. AIM: To evaluate the antihypertensive and vasorelaxant modes of action of a crude ethanolic extract from T. lucida aerial parts and to isolate the bioactive compounds. MATERIALS AND METHODS: Ethanolic extract was tested in an in vivo assay in SHR rats by intragastric administration at 10 and 100 mg/kg dosages, to measure and to compare hemodynamic parameters like diastolic and systolic blood pressure and heart rate. Also, extract (3.03-1000 µg/ml), fractions (3.03-1000 µg/ml) and pure isolated compounds (1.75-550 µM) were evaluated on isolated aortic rings contracted with noradrenaline (0.1 µM) to determine their vasorelaxant effect and extract-mode of action. RESULTS: Ethanolic extract of T. lucida lowered systolic and diastolic blood pressure on SHR rats without heart rate modification (P > 0.05). Moreover, the extract showed concentration-dependent relaxant effect in a partially endothelium-dependent manner (P < 0.05), through NO/cGMP system activation and calcium channel blockade. 6,7,8-trimethoxycoumarin (1), 6,7-dimethoxycoumarin (2), and 7-methoxycoumarin (3) from T. lucida are the main bioactive compounds of the extract and showed significant vasorelaxant activity. CONCLUSIONS: Results provide evidence and endorsed the antihypertensive properties attributed to T. lucida in traditional medicine, which is produced by vasorelaxant effect mainly through multitarget NO/cGMP system activation and calcium channel blockade. Coumarin derivatives 1, 2 and 3 are the responsible of the vasorelaxant activity.

Ruta Montana Evokes Antihypertensive Activity Through an Increase of Prostaglandins Release in L-NAME-Induced Hypertensive Rats.

AIMS: The aim of the study was to experimentally investigate the antihypertensive effect of Ruta Montana. BACKGROUND: Ruta montana L. is traditionally used in Moroccan herbal medicine to treat hypertension. This study aimed to experimentally evaluate the hypotensive and vasoactive properties of this plant. OBJECTIVE: The objective of the study was to evaluate the effect of the aqueous extract of Ruta Montana on blood pressure parameters in LNAME-induced hypertensive rats and to determine the vasorelaxant activity of this aqueous extract. METHODS: The antihypertensive effect of the aqueous extract obtained from Ruta montana aerial parts (RMAPAE) (200 mg/kg) was evaluated in normal and anesthetized hypertensive rats. Blood pressure parameters (systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure (DBP)) and heart rate were measured using a tail-cuff and a computer-assisted monitoring device. The acute and chronic effect of RMAPAE was recorded for 6 hours for the acute experiment and for 7 days for the sub-chronic test. In the other set, the vasorelaxant effect of RMAPAE on the contractile response was observed in the isolated thoracic aorta. RESULTS: The results indicated that the RMAPAE extract significantly decreased SBP, MBP, DBP and heart rate in L-NAME-induced hypertensive rats. Furthermore, RMAPAE was demonstrated to induce a dose-dependent relaxation in the aorta precontracted with Epinephrine or KCl. More interestingly, this vasorelaxant activity of RMAPAE seems to be probably mediated through the prostaglandins pathway. CONCLUSION: The present study illustrates the beneficial action of Ruta montana on hypertension and supports its use as an antihypertensive agent.

Ipomoea hederacea Jacq.: A plant with promising antihypertensive and cardio-protective effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Ipomoea hederacea Jacq. (family: Convolvulaceae) are traditionally used to treat high blood pressure and cardiac diseases. AIM OF THE STUDY: Present study was conducted to validate the traditional claim and explore the possible mechanism(s) of antihypertensive effects of I. hederacea. MATERIALS AND METHODS: Aqueous-ethanolic extract and activity based fractions of I. hederacea were evaluated using invasive blood pressure measuring technique, isolated tissue experiments, fructose induced hypertension/metabolic syndrome and biochemical analysis.Phytochemical analysis of active fraction was performed with aim to identify chemical composition of I. hederacea seeds. LC-MS analysis was also performed to identify the compounds proposed to be present in active fraction of I. hederacea seeds. RESULTS: Crude extract/fractions of I. hederacea showed dose (0.01-100 mg/kg) dependent significant hypotensive effect in normotensive anesthetized rats, similar to verapamil (0.01-30 mg/kg). Pretreatment with hexamethonium and atropine mediated no significant changes in hypotensive effect of butanol fraction of I. hederacea (Ih.Bn) at 3 mg/kg dose. However, a significant decrease in the hypotensive effect of Ih.Bn 3 mg/kg (-34.82 ± 3.36%; p < 0.05) was observed in the presence of L-NAME (20 mg/kg). Similarly, Ih.Bn (3 mg/kg) showed no significant effect on angiotensin-II response. However, response of phenylephrine (45.60 ± 9.63%; p < 0.05) and dobutamine (18.25 ± 2.10%; p < 0.01) was significantly decreased in the presence of Ih.Bn 3 mg/kg. Ih.Bn also exhibited dose dependent (0.01-100 mg/kg) antihypertensive effect in fructose induced hypertensive rats, similar to verapamil (0.01-30 mg/kg). Concomitant treatment with Ih.Bn (3, 10 and 30 mg/kg) for six weeks showed a dose dependent profound protection with significant (p < 0.01) effect at 30 mg/kg against fructose induced basal mean arterial pressure (142.2 ± 4.62 mmHg). Ih.Bn did not significantly change response of PE, Ang-II and Epi was observed in invasive and ex vivo techniques. However, Ih.Bn significantly (p < 0.01; p < 0.001) prevented against decrease in vascular response of acetylcholine in anesthetized rats and in isolated aorta of rat. A significant dose dependent decrease in triglyceride and glucose level (p < 0.001), and increase in HDL level (p < 0.05) was observed in Ih.Bn treated groups. Results of LC-MS analysis of Ih.Bn showed the presence of 24 compounds that belong to different chemical classes, including carboxylic acid, flavonoids, oligopeptides and tripeptide that are known to have antihypertensive and vasorelaxant properties. CONCLUSIONS: Results of present study indicate the presence of hypotensive/antihypertensive effect in crude extract/fractions of I. hederacea with most potent effect shown by butanol fraction (Ih.Bn), possibly mediated through α1 blocking, ß blocking and iNOS/cGMP stimulating activity.

Vhavenda Herbal Remedies as Sources of Antihypertensive Drugs: Ethnobotanical and Ethnopharmacological Studies.

Hypertension is a dominant risk factor for the development of cardiovascular, kidney, and eye diseases. In Africa, it increasingly leads to hospitalisation and a strain on the public health system. However, rather than modern medicine, African traditional healers are the first choice for most South Africans. Therefore, this study is aimed at gathering information on herbal remedies traditionally used for the treatment of high blood pressure in Vhavenda, South Africa, and comparing this information with reports in the literature regarding plants used to manage high blood pressure. An ethnobotanical survey was carried out in Vhembe district and its environs with 53 herbalists and indigenous people aged between 36 and 66 years from January to October 2019 using a semistructured questionnaire. The plants were collected with each respondent; they were authenticated and kept in herbarium. A total of 51 different plants were mentioned as being most commonly used for hypertension treatment. Of these, 44 plants were identified, with those from the Fabaceae family followed by plants from the Celastraceae family being commonly mentioned. Of these, the Elaeodendron transvaalense, Tabernaemontana elegans, Elephantorrhiza elephantina, and Aloe vossii were commonly cited species. According to the literature data, most of the identified plants are yet to be scientifically investigated for the treatment of hypertension, whereas only preliminary investigations have been carried out on other plants, suggesting that these preliminary investigations may have highlight promising antihypertensive activities in vitro that are indicative of their potential as antihypertensive drugs. Therefore, there is a need to scientifically investigate the antihypertensive potentials of these plants as a potential source of antihypertensive treatment and compounds.

Determination of l-(+)-bornesitol, the hypotensive constituent of Hancornia speciosa, in rat plasma by LC-MS/MS and its application on a pharmacokinetic study.

Hancornia speciosa is a medicinal plant with proven antihypertensive activity. The cyclitol l-(+)-bornesitol is the main constituent of its leaves and is a potent inhibitor of the angiotensin-converting enzyme. We herein investigated the pharmacokinetic properties of bornesitol administered orally to Wistar rats, as well as bornesitol permeation in Caco-2 cells. Bornesitol was isolated and purified from an ethanol extract of H. speciosa leaves. An ultra-high performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC-ESI-MS/MS) method was developed and validated to quantify bornesitol in rat plasma based on Multiple Reaction Monitoring, using pentaerythritol as an internal standard. Pharmacokinetics was evaluated by the administration of single doses via intravenous in bolus (3 mg/kg) and gavage (3, 15 and 25 mg/kg). Bornesitol permeation was assayed in a transwell Caco-2 cells model, tested alone, or combined with rutin, or as a constituent of H. speciosa extract, using a developed and validated UPLC-ESI-MS/MS method. All assayed validation parameters (selectivity, residual effect, matrix effect, linearity, precision, accuracy and stability of analyte in plasma and solution) for the bioanalytical method met the acceptance criteria established by regulatory guidelines. Bornestiol reached peak plasma concentration within approximately 60 min after oral administration with a half-life ranging from 72.15 min to 123.69 min. The peak concentration and area under the concentration-time curve of bornesitol did not rise proportionally with the increasing doses, suggesting a non-linear pharmacokinetics in rats and the oral bioavailability ranged from 28.5%-59.3%. Bornesitol showed low permeability in Caco-2 cells, but the permeability apparently increased when it was administered either combined with rutin or as a constituent of H. speciosa extract. In conclusion, bornesitol was rapidly absorbed after a single oral administration to rats and followed a non-linear pharmacokinetics. The obtained data will be useful to guide further pre-clinical development of bornesitol-containing herbal preparations of H. speciosa as an antihypertensive agent.

Studies to Elucidate the Mechanism of Cardio Protective and Hypotensive Activities of Anogeissus acuminata (Roxb. ex DC.) in Rodents.

Anogeissus acuminata (Roxb. ex DC.) is a folkloric medicinal plant in Asia; including Pakistan; used as a traditional remedy for cardiovascular disorders. This study was planned to establish a pharmacological basis for the trivial uses of Anogeissus acuminata in certain medical conditions related to cardiovascular systems and to explore the underlying mechanisms. Mechanistic studies suggested that crude extract of Anogeissus acuminata (Aa.Cr) produced in vitro cardio-relaxant and vasorelaxant effects in isolated paired atria and aorta coupled with in vivo decrease in blood pressure by invasive method; using pressure and force transducers connected to Power Lab Data Acquisition System. Moreover; Aa.Cr showed positive effects in left ventricular hypertrophy in Sprague Dawley rats observed hemodynamically by a decrease in cardiac cell size and fibrosis; along with absence of inflammatory cells; coupled with reduced levels of angiotensin converting enzyme (ACE) and renin concentration along with increased concentrations of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). In Acute Myocardial Infarction (AMI) model; creatine kinase (CK), creatine kinase-MB (CK-MB) and lactic acid dehydrogenase (LDH levels) were found to be decreased; along with decreased necrosis; edema and recruitment of inflammatory cells histologically. In vivo and ex vivo studies of Anogeissus acuminata provided evidence of vasorelaxant; hypotensive and cardioprotective properties facilitated through blockage of voltage-gated Ca++ ion channel; validating its use in cardiovascular diseases.

Geniposide in Gardenia jasminoides var. radicans Makino modulates blood pressure via inhibiting WNK pathway mediated by the estrogen receptors.

OBJECTIVES: To investigate the effects of geniposide in an iridoid found in Gardenia jasminoides var. radicans Makino (GJRM) in spontaneous hypertensive rat (SHR) and explore the possible mechanisms. METHODS: In this study, we detected the content of geniposide in GJRM by high-performance liquid chromatography (HPLC). Then, we used acute diuretic experiments to determine whether geniposide has diuretic effect. Moreover, we carried out experiments on SHR to further study the mechanism of hypertension, while real-time PCR, Western blot and immunohistochemistry were used for the experiments in vivo test. Hypotonic model was used for in vitro test. KEY FINDINGS: Our data showed that the content of geniposide in the extract of GJRM is 27.54%. Meanwhile, 50 mg/kg geniposide showed the strongest effect on promoting urine volume. Further study indicated that the extract of GJRM and geniposide could significantly reduce blood pressure and promote the excretion of urine and Na+ in SHR. In addition, geniposide significantly inhibited the activation of the with-no-lysine kinase (WNK) signalling pathway and significantly increases the protein expressions of estrogen receptor α (ERα), estrogen receptor ß (ERß) and G protein-coupled receptor 30 (GPR30) in SHR. In hypotonic model, geniposide significantly inhibits the phosphorylation of NKCC and NCC and could be antagonistic to estrogen receptor antagonists. CONCLUSIONS: Collectively, we would suggest that geniposide may potentially be utilized as an adjunct to existing thiazide and thiazide-like diuretics to control hypertension, mainly through inhibiting the activation of the WNK signalling pathway mediated by the estrogen receptor.

Effect of phenylacetamide isolated from lepidium apetalum on myocardial injury in spontaneously hypertensive rats and its possible mechanism.

Context: In the antihypertensive study of phenylacetamide (PA) on spontaneously hypertensive rats (SHR), it was occasionally found that PA prevents myocardial injury.Objective: Clarify the protective mechanism of PA on myocardial injury in SHR rats.Materials and methods: In vivo, SHR rats were treated with or without PA (15, 30, 45 mg/kg) for 3 weeks (12 per group). In vitro, H9c2 cells were treated with PA (1, 5, 10 µM) for 24 h, and then stimulated with H2O2 (300 µM) for 4 h. Molecular mechanisms were explored through cardiac pathology, cardiac function and biochemical markers.Results: In vivo, PA (15, 30, 45 mg/kg) reduced CVF from 14.8 ± 1.62 to 9.94 ± 1.56, 8.6 ± 1.33, 8.14 ± 1.45%; increased the LVEF relative level from 0.8 ± 0.06 to 0.83 ± 0.04, 0.86 ± 0.05, 0.9 ± 0.04. All three doses can improve the cardiac pathological structure and function (LVEDD, LVESD, LVFS, heart index, NT-proBNP, CKMB, SBP); however, 45 mg/kg works best. But different doses show different molecular mechanisms. PA (15 mg/kg) improves RAAS system (REN, ACE), inflammation (ET-1, IL-1ß) and MAPK pathway (p-ERK/ERK, p-JNK/JNK) better. PA (45 mg/kg) improves oxidative stress (SOD, NOX1) and TGF-ß pathway (Smad3) better. In vitro, PA improved cell viability, oxidative stress (SOD, NOX1) and Smad3 protein expression.Discussion and conclusions: PA regulates different mechanisms at different concentrations to improve myocardial injury, and high dose is the best. This experiment provides a theoretical basis for the development of new clinical drugs for cardiovascular disease.