Extract of Chenopodium album lowers blood pressure in rats through endothelium-dependent and -independent vasorelaxation.

OBJECTIVES: To investigate the antihypertensive effect of crude extract of Chenopodium album (Ca.Cr), based on its medicinal use in hypertension. METHODS: Ca.Cr and its fractions were tested in-vivo in normotensive anesthetized rats for blood pressure-lowering effect. In-vitro experiments were performed on isolated rat aortae to explore the vascular mechanism(s). RESULTS: In normotensive anesthetized rats, Ca.Cr produced a dose-dependent (1-300mg/kg) fall (30%mmHg) in mean arterial pressure (MAP). Among the fractions, nHexane was the most potent (46% fall). In rat aortic rings precontracted with phenylephrine (PE), Ca.Cr and its fractions (except Ca.Aq) produced endothelium-dependent vasorelaxation, which was partially reversed with endothelium removal and by pretreating intact aortic rings with L-NAME (10µM) and atropine (1µM). This relaxation to Ca.Cr and fractions (nHexane, ethylacetate and chloroform) was also eliminated with indomethacin pretreatment, however, it unmasked a vasoconstriction effect with Ca.Cr only. Surprisingly, the aqueous fraction produced a calcium sensitive strong vasoconstriction instead of vasorelaxation. The crude extract and its fractions (except Ca.Aq) also antagonized vasoconstriction induced with high K+ (80mM), suggesting calcium antagonistic effect. The aqueous fraction produced mild vasorelaxation against high K+. This effect was further confirmed when pretreatment of the aortic rings with different concentrations of crude extract and fractions suppressed CaCl2 concentration response curves, similar to verapamil. In acute toxicity test, Ca.Cr extract was found safe up to 5g/kg body weight in mice. CONCLUSION: These findings suggest that crude extract and fractions of C. album produced vasorelaxant effect through muscarinic receptors linked-NO pathway, prostaglandin (endothelium-dependent) and calcium antagonism (endothelium-independent), which explains the blood pressure lowering effect of C. album in rats.

7-Hydroxy Frullanolide Ameliorates Isoproterenol-Induced Myocardial Injury through Modification of iNOS and Nrf2 Genes.

Myocardial infarction (MI) is the principal cause of premature death. Protecting myocardium from ischemia is the main focus of intense research. 7-hydroxy frullanolide (7-HF) is a potent anti-inflammatory agent, showing its efficacy in different acute and chronic inflammatory disorders such as atherosclerosis, suggesting it can be a potential cardioprotective agent. For the induction of MI, Sprague-Dawley rats (n = 5) were administered isoproterenol (ISO) 85 mg/kg s.c at 24 h intervals for two days. The potential cardioprotective effect of 7-HF and its mechanisms were explored by in vivo and in vitro methods. 7-HF significantly prevented the extent of myocardial injury by decreasing the infarct size, preserving the histology of myocardial tissue, and reducing the release of cardiac biomarkers. Further, 7-HF increased the mRNA expression of cardioprotective gene Nrf2 and reduced the mRNA expression of iNOS. 7-HF also improved cardiac function by decreasing the cardiac workload through its negative chronotropic and negative ionotropic effect, as well as by reducing peripheral vascular resistance due to the inhibition of voltage-dependent calcium channels and the release of calcium from intracellular calcium stores. In conclusion, 7-HF showed cardioprotective effects in the MI model, which might be due to modulating the expression of iNOS and Nrf2 genes as well as improving cardiac functions.

Antioxidant Flavonoid Diosmetin Is Cardioprotective in a Rat Model of Myocardial Infarction Induced by Beta 1-Adrenergic Receptors Activation.

Myocardial infarction (MI) is a common and life-threatening manifestation of ischemic heart diseases (IHD). The most important risk factor for MI is hypertension. Natural products from medicinal plants have gained considerable attention globally due to their preventive and therapeutic effects. Flavonoids have been found to be efficacious in ischemic heart diseases (IHD) by alleviating oxidative stress and beta-1 adrenergic activation, but the mechanistic link is not clear. We hypothesized that antioxidant flavonoid diosmetin is cardioprotective in a rat model of MI induced by beta 1-adrenergic receptor activation. To test this hypothesis, we evaluated the cardioprotective potential of diosmetin on isoproterenol-induced MI in rats by performing lead II electrocardiography (ECG), cardiac biomarkers including troponin I (cTnI) and creatinine phosphokinase (CPK), CK-myocardial band, (CK-MB), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotranferase (AST) by using biolyzer 100, as well as histopathological analysis. We found that diosmetin (1 and 3 mg/kg) attenuated isoproterenol-induced elevation in the T-wave and deep Q-wave on the ECG, as well as heart-to-body weight ratio and infarction size. In addition, pretreatment with diosmetin attenuated the isoproterenol-induced increase in serum troponin I. These results demonstrate that flavonoid diosmetin may provide therapeutic benefit in myocardial infarction.

Synthesis and characterization of biologically active flurbiprofen amide derivatives as selective prostaglandin-endoperoxide synthase II inhibitors: In vivo anti-inflammatory activity and molecular docking.

A novel series of twenty two flurbiprofen amides (1-22) were designed and synthesized in good to excellent yields by reacting flurbiprofen acid with various aromatic/aliphatic primary amines in the presence of 1,1­carbonyldiimidazole (CDI) in basic medium using acetonitrile as solvent. Structures of the synthesized derivatives were elucidated with the help of HR-ESI-MS, 1H-, and 13C NMR spectroscopy and finally screened them for their in-vivo anti-inflammatory potential using carrageenan induced mice paw oedema assay. Among the series, four compounds (8, 14, 15, and 20) displayed excellent activity ranging from 59.0 to 77.7 % decrease, while eight compounds (1, 3, 7, 10, 12, 13, 17, and 18) exhibited good activity in the decrease range of 37.0-50.0 %. Additionally, four compounds (2, 6, 16, and 22) attributed less activity, while the remaining six compounds (4, 5, 9, 11, 19, and 21) were found to be inactive. Furthermore, the In-silico studies were executed on the synthesized derivatives in order to explain the binding interface of compounds with the active sites of prostaglandin endoperoxide-synthase II enzyme.

Vasorelaxant and Antihypertensive Effects of Bergenin on Isolated Rat Aorta and High Salt-Induced Hypertensive Rats.

Bergenin is a phenolic glycoside that has been reported to be present in some medicinal plants which are traditionally used for their antihypertensive actions. So, bergenin was investigated for antihypertensive and vasorelaxant experiments in a rat model. Bergenin produced a significant fall in the mean arterial pressure (MAP) of rats. To explore the involvement of NO and muscarinic receptors, rats were pretreated with L-NAME and atropine in-vivo. The L-NAME did not change significantly the effect of bergenin on MAP excluding the involvement of NO. Unlike the L-NAME, atropine pretreatment reduced the effect of bergenin on MAP, indicating the role of muscarinic receptors. In in-vitro study, the bergenin produced endothelium-dependent (at lower concentrations) and independent (at higher concentrations) vasorelaxation, which was attenuated significantly in the presence of atropine and indomethacin but not with L-NAME. While a partial response was observed against K+-induced contractions. This was further confirmed when bergenin partly shifted the CaCl2-CRCs toward right. Bergenin also suppressed the PE peak formation, indicating the antagonist effect against the release of Ca2+. Moreover, the bergenin-induced vasorelaxant response was not markedly attenuated with TEA, while significantly ablated with 4-AP and BaCl2. In conclusion, the antihypertensive effects of bergenin are due to Ca2+ channel blockade, K+ channels activation, and muscarinic receptor-linked vasodilation.

LC-MS/MS-Based Metabolomic Profiling of Constituents from Glochidion velutinum and Its Activity against Cancer Cell Lines.

This study aimed to establish the phytochemical profile of Glochidion velutinum and its cytotoxic activity against prostate cancer (PC-3) and breast cancer (MCF-7) cell lines. The phytochemical composition of G. velutinum leaf extract and its fractions was established with the help of total phenolic and flavonoid contents and LC-MS/MS-based metabolomics analysis. The crude methanolic extract and its fractions were studied for pharmacological activity against PC-3 and MCF-7 cell lines using the MTT assay. The total phenolic content of the crude extract and its fractions ranged from 44 to 859 µg GAE/mg of sample whereas total flavonoid contents ranged from 20 to 315 µg QE/mg of sample. A total of forty-eight compounds were tentatively dereplicated in the extract and its fractions. These phytochemicals included benzoic acid derivatives, flavans, flavones, O-methylated flavonoids, flavonoid O- and C-glycosides, pyranocoumarins, hydrolysable tannins, carbohydrate conjugates, fatty acids, coumarin glycosides, monoterpenoids, diterpenoids, and terpene glycosides. The crude extract (IC50 = 89 µg/mL), the chloroform fraction (IC50 = 27 µg/mL), and the water fraction (IC50 = 36 µg/mL) were found to be active against the PC-3 cell line. However, the crude extract (IC50 = 431 µg/mL), the chloroform fraction (IC50 = 222 µg/mL), and the ethyl acetate fraction (IC50 = 226 µg/mL) have shown prominent activity against breast cancer cells. Moreover, G. velutinum extract and its fractions presented negligible toxicity to normal macrophages at the maximum tested dose (600 µg/mL). Among the compounds identified through LC-MS/MS-based metabolomics analysis, epigallocatechin gallate, ellagic acid, isovitexin, and rutin were reported to have anticancer activity against both prostate and breast cancer cell lines and might be responsible for the cytotoxic activities of G. velutinum extract and its bioactive fractions.

Antihypertensive Potential of Tartaric Acid and Exploration of Underlying Mechanistic Pathways.

Tartaric acid is capable of balancing blood pressure. It is the main constituent of antihypertensive agents (grapes and wine) and has not been scientifically explored as an antihypertensive remedy. This study aimed to investigate the antihypertensive effect of a low-dose tartaric acid in vivo and explore underlying mechanisms in vitro. Intravenous administration of tartaric acid at the dose of 50 µg/kg caused a % fall in mean arterial pressure (MAP) in normotensive and hypertensive rats [51.5 ± 1.7 and 63.5 ± 2.9% mmHg]. This hypotensive effect was partially inhibited by atropine (1 mg/kg) and L-NAME (100 µg/kg) pretreatment. In hypertensive rats, oral administration of tartaric acid (.1, .5, 1, 5, and 10 mg/kg) for 2 weeks resulted in 65 ± 7.3 mmHg MAP at 10 mg/kg. This antihypertensive effect was comparable to the orally administered verapamil (10 mg/kg) for 2 weeks which caused a decrease in MAP 60.4 ± 3.8 mmHg. Tartaric acid relaxed phenylephrine (PE) and High K+-induced contractions with EC50 values of .157 (.043-.2) and 1.93 (.07-2) µg/mL in vitro. This endothelium-dependent relaxation was inhibited with atropine (1 µM) and L-NAME (10 µM) pretreatment. Tartaric acid also suppressed phenylephrine contractions in Ca+2 free/EGTA medium and on voltage-dependent calcium channels, causing the concentration-response curves toward right. Tartaric acid induced negative inotropic and chronotropic effects with EC50 values of .26 (.14-.4) and .60 (.2-.8) in rat atria. It showed its effect by complete blockade against atropine and partially in propranolol pretreatment. These findings provide scientific basis to low-dose tartaric acid as an antihypertensive and vasodilatory remedy through muscarinic receptor-linked nitric oxide (NO) pathway and Ca+2 channel antagonist.

Investigation into the Antihypertensive Effects of Diosmetin and Its Underlying Vascular Mechanisms Using Rat Model.

OBJECTIVE: Diosmetin is a flavonoid that is found in many important medicinal plants that have antihypertensive therapeutic potential. Diosmetin has been shown to have antiplatelet, anti-inflammatory and antioxidant properties, which suggests that it could be a potential candidate for use in antihypertensive therapy. METHODS: In vivo and in vitro methods were used for our investigation into the antihypertensive effects of diosmetin. RESULTS: Diosmetin significantly decreased the mean arterial pressure (MAP). The effects of diosmetin on the MAP and heart rate were more pronounced in hypertensive rats. To explore the involvement of the muscarinic receptors-linked NO pathway, Nω-nitro-L-arginine methyl ester (L-NAME) and atropine were pre-administered in vivo. The pretreatment with L-NAME did not significantly change the effects of diosmetin on the MAP by excluding the involvement of NO. Unlike L-NAME, the atropine pretreatment reduced the effects of diosmetin on the MAP, which demonstrated the role of the muscarinic receptors. In the in vitro study, diosmetin at lower concentrations produced endothelium-dependent and -independent (at higher concentrations) vasorelaxation, which was attenuated significantly by the presence of atropine and indomethacin but not L-NAME. Diosmetin was also tested for high K+-induced contractions. Diosmetin induced significant relaxation (similar to verapamil), which indicated its Ca2+ antagonistic effects. This was further confirmed by diosmetin shifting the CaCl2 CRCs toward the right due to its suppression of the maximum response. Diosmetin also suppressed phenylephrine peak formation, which indicated its antagonist effects on the release of Ca2+. Moreover, BaCl2 significantly inhibited the effects of diosmetin, followed by 4-AP and TEA, which suggested that the K+ channels had a role as well. CONCLUSIONS: The obtained data showed the Ca2+ channel antagonism, potassium channel activation and antimuscarinic receptor-linked vasodilatory effects of diosmetin, which demonstrated its antihypertensive potential.

Antihypertensive Activity in High Salt-Induced Hypertensive Rats and LC-MS/MS-Based Phytochemical Profiling of Melia azedarach L. (Meliaceae) Leaves.

Melia azedarach L. leaves have been traditionally used but not scientifically evaluated for antihypertensive activity. The focus of the present work was to carry out the detailed phytochemical profiling and antihypertensive potential of methanolic extract and subsequent fractions of this plant. The tandem mass spectrometry-based phytochemical profiling of M. azedarach extract (Ma.Cr) and fractions was determined in negative ionization mode while molecular networking was executed using the Global Natural Product Social (GNPS) molecular networking platform. This study resulted in the identification of 29 compounds including flavonoid O-glycosides, simple flavonoids, triterpenoidal saponins, and cardenolides as the major constituents. Ma.Cr at the concentration of 300 mg/kg resulted in a fall in blood pressure (BP), i.e., 81.44 ± 2.1 mmHg in high salt-induced hypertensive rats in vivo, in comparison to normotensive group, i.e., 65.36 ± 1.8 mmHg at the same dose. A decrease in blood pressure was observed in anaesthetized normotensive and hypertensive rats treated with extract and various fractions of M. azedarach. A reasonable activity was observed for all fractions except the aqueous fraction. The highest efficacy was shown by the ethyl acetate fraction, i.e., 77.06 ± 3.77 mmHg in normotensive and 88.96 ± 1.3 mmHg in hypertensive anaesthetized rats. Ma.Cr and fractions showed comparatively better efficacy towards hypertensive rats as compared to rats with normal blood pressure. Blood pressure-lowering effects did not change upon prior incubation with atropine. In vitro testing of Ma.Cr and polarity-based fractions resulted in L-NAME sensitive, endothelium-dependent vasodilator effects on aortic tissues. Pretreatment of aorta preparations with Ma.Cr and its fractions also blocked K+-induced precontractions indicating Ca2+ channel blocking activity comparable to verapamil. The extract and polarity-based fractions did not reveal a vasoconstrictor response in spontaneously beating isolated rat aorta. Ma.Cr and fractions when used in atrial preparations resulted in negative inotropic and chronotropic effects. These effects in atrial preparations did not change in the presence of atropine. These effects of extract and fractions explained the antihypertensive potential of M. azedarach and thus provided a scientific basis for its ethnopharmacological use in the treatment of hypertension. Among the constituents observed, flavonoids and flavonoid O-glycosides were previously reported for antihypertensive potential.

Juglone from Walnut Produces Cardioprotective Effects against Isoproterenol-Induced Myocardial Injury in SD Rats.

Therapeutic and/or preventive interventions using phytochemical constituents for ischemic heart disease have gained considerable attention worldwide, mainly due to their antioxidant activity. This study investigated the cardioprotective effect and possible mechanism of juglone, a major constituent of the walnut tree, using an isoproterenol (ISO)-induced myocardial infarction (MI) model in rats. Rats were pretreated for five (5) days with juglone (1, 3 mg/kg, i.p) and atenolol (1 mg/kg, i.p) in separate experiments before inducing myocardial injury by administration of ISO (80 mg/kg, s.c) at an interval of 24 h for 2 consecutive days (4th and 5th day). The cardioprotective effect of juglone was confirmed through a lead II electrocardiograph (ECG), cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological study. The results of our present study suggest that prior administration of juglone (1 and 3 mg/kg) proved to be effective as a cardioprotective therapeutic agent in reducing the extent of myocardial damage (induced by ISO) by fortifying the myocardial cell membrane, preventing elevated T-waves, deep Q-waves in the ECG, heart to body weight ratio, infarction and also by normalizing cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological changes, such as inflammation, edema and necrosis. In conclusion, this study has identified phytochemical constituents, in particular juglone, as a potential cardioprotective agent.

Cardioprotective Potential of Aqueous Extract of Fumaria indica on Isoproterenol-Induced Myocardial Infarction in SD Rats.

Ischemic heart disease (IHD) treatments and preventions by using plant extract and its phytochemical constituents have achieved considerable attention globally due to its cardioprotective effects. This study is aimed at investigating the cardioprotective and vascular effects of Fumaria indica (F. indica) crude extract on isoproterenol- (ISO-) induced myocardial infarction (MI) in Sprague-Dawley (SD) rats. Rats treated with isoproterenol (85 mg/kg, s.c), administered. Twice at an interval of 24 h showed a significant ST-segment elevation in ECG, edema, and necrosis in histopathology and also in troponin I (cTnI), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST). Pretreatment with F. indica (10, 30, and 100 mg/kg, p.o) for 21 days significantly reversed the effects of isoproterenol-induced ischemic changes in the ECG, levels of cTnI, CPK, LDH, and AST, and histopathological changes. In isolated rat atrial strips, F. indica induced negative chronotropic and inotropic effects which were not affected by pretreatment with atropine, excluding role of cardiac muscarinic receptors. Cumulative addition of the extract induced a vasorelaxant effect on phenylephrine-evoked contractions in isolated rat aortic rings, which remained unchanged when challenged with L-NAME, excluding role of endothelial NO. However, extract of F. indica concentration dependently reversed contractions evoked with high K+, indicating calcium entry blocking effect. In conclusion, the F. indica extract is a cardioprotective remedy that ameliorates the isoproterenol-induced cardiotoxic effects and reverses cardiac ischemia, and the calcium antagonistic effect might be of useful in the treatment of MI.

Antihypertensive effect and the underlying mechanisms of action of phytolaccagenin in rat models.

BACKGROUND: Phytolaccagenin, a natural triterpenoid, is reported for various biological activities that indicate its potential role in the management of hypertension. METHODS: Phytolaccagenin was evaluated for its antihypertensive activity in rat models via in vivo and in vitro experiments using polyethylene tubings for cannulation, organ bath bubbled with carbogen gas, and a pressure transducer connected to a PowerLab data acquisition system. RESULTS: Intravenous administration of phytolaccagenin decreased mean arterial pressure (MAP), significantly, in normotensive and hypertensive anesthetized rats. Pretreatment of rats with atropine (2 mg/kg) partially reversed the decrease in blood pressure due to phytolaccagenin at first tested doses. However, Nω-nitro-L-arginine methyl ester (L-NAME) (100 mg/kg) pretreatment modified the effect of phytolaccagenin on blood pressure with greater response. In isolated rat aortic rings precontracted with phenylephrine, cumulative addition of phytolaccagenin induced relaxation that is ablated (50%) with denudation and pre-incubation with atropine (1 µM) and L-NAME (10 µM). Phytolaccagenin also partially inhibited high K+ precontraction at initial doses, while an inhibitory effect was observed at higher concentrations, confirming its effect on voltage-dependent calcium channels. In isolated spontaneously beating rat atrial strips, phytolaccagenin suppressed the atrial tone that was reduced with isoprenaline and atropine pre-incubation, suggesting the role of cardiac adrenergic and muscarinic receptors. Interestingly, atenolol (1 µM) pretreatment also ablated the cardiac effects of phytolaccagenin. CONCLUSION: The antihypertensive effect of phytolaccagenin is due to a decrease in vascular resistance and cardiac depressant effects. These effects are mediated via muscarinic receptors-linked NO pathway, inhibitory effect on Ca2+ movements (vascular), and activation of cardiac muscarinic and blockade of ß-adrenergic receptors.

Tandem high resolution mass spectrometry based phytochemical composition of Sauromatum guttatum tubers and its enzyme inhibitory potential with molecular docking.

Sauromatum guttatum has been traditionally used in the treatment of snakebite and tumors in India, Pakistan, and China. However, it lacks detailed phytochemical composition like other members of the family Araceae. Therefore, the aim of the present study was to investigate the phytochemical composition of crude methanolic extract and subsequent fractions from S. guttatum tubers and to determine their enzyme inhibitory potentials. The phytochemical profile was studied through tandem high-resolution mass-based phytochemical analysis and Global Natural Product Social (GNPS) molecular networking. Similarly, crude extract and fractions were also investigated for enzyme inhibitory activity against urease and α-glucosidase. Twenty-six compounds were dereplicated belonging to flavone C-glycosides, flavone O-glycosides, phenolic acids, phenolic acid glycosides, and iridoid glycosides. The n-butanol fraction was particularly found rich in flavone di-C-glycosides including schaftoside, isoschaftoside, neoschaftoside, and vicenin-2. The n-butanol fraction exhibited the highest in vitro inhibition against urease and α-glucosidase with IC50 values of 113.7 µg/mL and 155.3 µg/mL, respectively. The results of enzyme inhibition potential were also supported by in silico molecular docking studies against the above-mentioned enzymes. This is the first report on the detailed phytochemical profile of S. guttatum tubers, and these results will contribute to the chemosystematic knowledge of the Araceae family. The results of this study also suggest that S. guttatum may find possible applications in the treatment of gastrointestinal disorders and diabetes.

DNA methylation across the tree of life, from micro to macro-organism.

DNA methylation is a process in which methyl (CH3) groups are added to the DNA molecule. The DNA segment does not change in the sequence, but DNA methylation could alter the action of DNA. Different enzymes like DNA methyltransferases (DNMTs) take part in methylation of cytosine/adenine nucleosides in DNA. In prokaryotes, DNA methylation is performed to prevent the attack of phage and also plays a role in the chromosome replication and repair. In fungi, DNA methylation is studied to see the transcriptional changes, as in insects, the DNA methylation is not that well-known, it plays a different role like other organisms. In mammals, the DNA methylation is related to different types of cancers and plays the most important role in the placental development and abnormal DNA methylation connected with diseases like cancer, autoimmune diseases, and rheumatoid arthritis.

Evaluation of the Antiasthmatic Activity of Carissa opaca in Animal Models.

Carissa opaca Stapf ex Haines (C. opaca) fruit is used traditionally in the treatment of respiratory illnesses including asthma. However, there is no scientific evidence supporting its antiasthmatic activity. The current study was conducted to evaluate its antiasthmatic effects using in vivo and in vitro approaches. The methanolic crude extract of C. opaca fruit (Co.Cr.) was used and in vivo antiasthmatic activity was carried out using ovalbumin- (OVA-) sensitized and OVA-challenged BALB/c mice. In in vitro bronchorelaxant activity of crude extract, aqueous and n-hexane fractions of C. opaca were carried out on isolated rat tracheal strips. Co.Cr. (200 and 400 mg/kg) attenuated ovalbumin-induced changes in lung histochemistry with % decrease in peribronchial inflammation of 14.1 ± 0.21 and 65.8 ± 0.22 and % decrease in total inflammatory cell count of 35.7 ± 2.80 and 53.3 ± 2.30 in bronchoalveolar lavage fluid. Co.Cr., aqueous, and n-hexane fraction of C. opaca attenuated the precontractions induced by high K+ (80 mM) and carbachol (1 µM), respectively. In conclusion, the results showed that C. opaca possesses antiasthmatic activity via relaxant effect on bronchial smooth muscle which is mediated through calcium channel blockade and antimuscarinic activity. This study provides scientific evidence of the traditional use of C. opaca in the management of allergic asthma.

O Efeito Anti-Hipertensivo de Sauromatum Guttatum Mediado por Efeitos Vasorrelaxante e Depressivos Miocárdicos / Antihypertensive Activity of Sauromatum guttatum Mediated by Vasorelaxation and Myocardial Depressant Effects

Resumo Fundamento: A Sauromatum guttatum (S. guttatum) é utilizado no tratamento de doenças do sangue e supostamente tem atividade espasmolítica através da inibição dos canais de Ca2+. Objetivos: O objetivo deste estudo foi investigar o potencial anti-hipertensivo de S. guttatum em modelo de rato Sprague-Dawley (SD) com hipertensão induzida por dieta com alto teor de sal (HIDATS). Métodos: Ratos SD foram divididos em normotensos, hipertensos e grupos tratados com verapamil e S. guttatum. Extrato bruto de S. guttatum (Sg.B) (100, 150 e 300 mg/kg/dia) e verapamil (5, 10 e 15 mg/kg/dia) foram administrados por via oral junto com NaCl. Anéis aórticos e faixas do átrio direito de ratos normotensos foram utilizados para investigar os mecanismos subjacentes. O nível de significância estatística adotado foi de 5%. Resultados: A pressão arterial média diminuiu nos grupos hipertensos tratados com Sg.B e verapamil de forma dose-dependente (p <0,001). No estudo de reatividade vascular, a acetilcolina induziu relaxamentos com valor CE50 de 0,6 µg/mL (0,3-1,0) em ratos hipertensos tratados com Sg.B (300 mg/kg), sugerindo preservação endotelial. Em aorta isolada de rato normotenso, o Sg.B exibiu vasorrelaxamento com valor de CE50 de 0,15 mg/mL (0,10-0,20), após ablação por desnudamento endotelial ou pré-tratamento com L-NAME e atropina. O tratamento com Sg.B causou relaxamento contra contrações induzidas por K+ alto, como o verapamil. O Sg.B mostrou efeitos inotrópicos (82%) e cronotrópicos (56%) negativos em preparações isoladas atriais de ratos reduzidas com atropina. A avaliação fitoquímica indicou a presença de alcaloides, flavonoides e taninos. Conclusão: O S. guttatum possui efeito vasodilatador através da preservação da função endotelial, liberação de NO mediada pelo receptor muscarínico e inibição do movimento de Ca2+, enquanto o efeito depressor do miocárdio atrial pode estar ligado ao receptor muscarínico. Esses achados fornecem a base farmacológica para o uso do extrato de S. guttatum como um medicamento anti-hipertensivo.

Abstract Background: Sauromatum guttatum (S. guttatum) is used in the treatment of blood disorders and reportedly has a spasmolytic activity through Ca2+ channel inhibition. Objectives: The aim of this study was to investigate the antihypertensive potential of S. guttatum in high salt-induced hypertensive Sprague-Dawley (SD) rat model (HSHRs). Methods: SD rats were divided into normotensive, hypertensive, S. guttatum and verapamil treated groups. S. guttatum crude extract (Sg.Cr) (100, 150 and 300 mg/kg/day) and verapamil (5, 10 and 15 mg/kg/day) were administered orally along with NaCl. Aortic rings and right atrial strips from normotensive rats were used to investigate the underlying mechanisms. The level of statistical significance was set at 5%. Results: Mean arterial pressure decreased in the Sg.Cr and verapamil-treated hypertensive groups in a dose-dependent manner (p < 0.001). In the vascular reactivity study, acetylcholine induced relaxations with an EC50 value of 0.6 µg/mL (0.3-1.0) in Sg.Cr-treated hypertensive rats (300 mg/kg), suggesting endothelial preservation. In isolated normotensive rat aorta, Sg.Cr-treated rats showed vasorelaxation with an EC50 value of 0.15 mg/mL (0.10-0.20), ablated by endothelial denudation or pretreatment with L-NAME and atropine. Sg.Cr treatment caused relaxation against high K+-induced contractions, like verapamil. Sg.Cr showed negative inotropic (82%) and chronotropic effects (56%) in isolated rat atrial preparations reduced with atropine. The phytochemical investigation indicated presence of alkaloids, flavonoids and tannins. Conclusion: S. guttatum has a vasodilatory effect through endothelial function preservation, muscarinic receptor-mediated NO release and Ca2+ movement inhibition, while atrial myocardial depressant effect can be linked to the muscarinic receptor. These findings provide pharmacological base for using S. guttatum extract as an antihypertensive medication.

Insight into the cardiovascular mechanisms of blood pressure lowering effect of gitogenin: a steroidal saponin.

Background/objectives: Steroidal saponins are widely distributed in medicinal plants with potential applications in cardiovascular disorders. Gitogenin, a saponin, has not been explored as antihypertensive; this investigation was aimed to explore its blood pressure lowering potential and underlying mechanisms.Methodology: The effect of gitogenin was evaluated on blood pressure in vivo, using normotensive rat model and the underlying cardiovascular mechanism(s) in vitro, in isolated rat aorta and in atria preparations using PowerLab data acquisition system (ADInstrument, Australia).Results: Intravenous injection of gitogenin decreased mean arterial pressure (MAP) in anesthetized rats. Atropine (1 mg/kg) and L-NAME (100 mg/kg) pretreatment significantly (*p < .05) attenuated effect on MAP to gitogenin. In isolated intact aortic rings, gitogenin induced endothelium-dependent vasodilatation (maximum 65%), which was ablated (maximum 22%) with L-NAME (100 mg/kg) and atropine (1 µM) pretreatment or endothelium removal. Gitogenin was found more potent against angiotensin II precontractions without effect on high K+ and low K+ precontractions. In isolated rat right atria, gitogenin suppressed rate and force of contractions. Atropine (1 µM) pretreatment partially inhibited effect of gitogenin on force and eliminated its effect on rate. Combined atropine (10 µM) and atenolol (0.5 µM) pretreatment was without effect on force of contractions but eliminated effect of gitogenin on rate with 25% increase.Conclusion: These findings indicate that antihypertensive effect of gitogenin is the outcome of vascular and cardiac effects; agonistic effect on vascular M3 and cardiac M2 receptors; and being more selective for M2. Increase in the rate of atrial contraction might be of clinical importance.

Assessing the ethnobotanical potential of Carissa opaca berries by merging outcomes from metabolomics profiling, enzyme assays, and in silico docking studies.

The phytochemical profile of Carissa opaca fruit extract and fractions was established through dereplication strategies employing LC-MS/MS and global natural product social molecular networking (GNPS). Crude extract and fractions were evaluated for their potential to inhibit α-glucosidase and urease in vitro. Flavonoid-O-glycosides, flavonoid-C-glycosides, flavonoids, proanthocyanidin B2, phenolics, and triterpenoids were annotated as the major classes of secondary metabolites present in the extract and fractions. α-Glucosidase inhibition was associated with n-butanol and ethyl acetate fractions comparable to acarbose (IC50 = 120.43 µg/mL) with IC50 values of 123.67 and 131.72 µg/mL, respectively. The ethyl acetate fraction showed good urease inhibition comparable with thiourea (IC50 = 103.71 µg/mL) with an IC50 value of 109.14 µg/mL. Molecular docking studies of compounds observed in the crude extract and bioactive fractions had significant binding scores, which supported results for enzyme inhibition in vitro. This study provided a detailed phytochemical profile of C. opaca fruit and its enzyme inhibition potential.

Antihypertensive Activity of Sauromatum guttatum Mediated by Vasorelaxation and Myocardial Depressant Effects. / O Efeito Anti-Hipertensivo de Sauromatum Guttatum Mediado por Efeitos Vasorrelaxante e Depressivos Miocárdicos.

BACKGROUND: Sauromatum guttatum (S. guttatum) is used in the treatment of blood disorders and reportedly has a spasmolytic activity through Ca2+ channel inhibition. OBJECTIVES: The aim of this study was to investigate the antihypertensive potential of S. guttatum in high salt-induced hypertensive Sprague-Dawley (SD) rat model (HSHRs). METHODS: SD rats were divided into normotensive, hypertensive, S. guttatum and verapamil treated groups. S. guttatum crude extract (Sg.Cr) (100, 150 and 300 mg/kg/day) and verapamil (5, 10 and 15 mg/kg/day) were administered orally along with NaCl. Aortic rings and right atrial strips from normotensive rats were used to investigate the underlying mechanisms. The level of statistical significance was set at 5%. RESULTS: Mean arterial pressure decreased in the Sg.Cr and verapamil-treated hypertensive groups in a dose-dependent manner (p < 0.001). In the vascular reactivity study, acetylcholine induced relaxations with an EC50 value of 0.6 µg/mL (0.3-1.0) in Sg.Cr-treated hypertensive rats (300 mg/kg), suggesting endothelial preservation. In isolated normotensive rat aorta, Sg.Cr-treated rats showed vasorelaxation with an EC50 value of 0.15 mg/mL (0.10-0.20), ablated by endothelial denudation or pretreatment with L-NAME and atropine. Sg.Cr treatment caused relaxation against high K+-induced contractions, like verapamil. Sg.Cr showed negative inotropic (82%) and chronotropic effects (56%) in isolated rat atrial preparations reduced with atropine. The phytochemical investigation indicated presence of alkaloids, flavonoids and tannins. CONCLUSION: S. guttatum has a vasodilatory effect through endothelial function preservation, muscarinic receptor-mediated NO release and Ca2+ movement inhibition, while atrial myocardial depressant effect can be linked to the muscarinic receptor. These findings provide pharmacological base for using S. guttatum extract as an antihypertensive medication.

FUNDAMENTO: A Sauromatum guttatum (S. guttatum) é utilizado no tratamento de doenças do sangue e supostamente tem atividade espasmolítica através da inibição dos canais de Ca2+. OBJETIVOS: O objetivo deste estudo foi investigar o potencial anti-hipertensivo de S. guttatum em modelo de rato Sprague-Dawley (SD) com hipertensão induzida por dieta com alto teor de sal (HIDATS). MÉTODOS: Ratos SD foram divididos em normotensos, hipertensos e grupos tratados com verapamil e S. guttatum. Extrato bruto de S. guttatum (Sg.B) (100, 150 e 300 mg/kg/dia) e verapamil (5, 10 e 15 mg/kg/dia) foram administrados por via oral junto com NaCl. Anéis aórticos e faixas do átrio direito de ratos normotensos foram utilizados para investigar os mecanismos subjacentes. O nível de significância estatística adotado foi de 5%. RESULTADOS: A pressão arterial média diminuiu nos grupos hipertensos tratados com Sg.B e verapamil de forma dose-dependente (p <0,001). No estudo de reatividade vascular, a acetilcolina induziu relaxamentos com valor CE50 de 0,6 µg/mL (0,3­1,0) em ratos hipertensos tratados com Sg.B (300 mg/kg), sugerindo preservação endotelial. Em aorta isolada de rato normotenso, o Sg.B exibiu vasorrelaxamento com valor de CE50 de 0,15 mg/mL (0,10-0,20), após ablação por desnudamento endotelial ou pré-tratamento com L-NAME e atropina. O tratamento com Sg.B causou relaxamento contra contrações induzidas por K+ alto, como o verapamil. O Sg.B mostrou efeitos inotrópicos (82%) e cronotrópicos (56%) negativos em preparações isoladas atriais de ratos reduzidas com atropina. A avaliação fitoquímica indicou a presença de alcaloides, flavonoides e taninos. CONCLUSÃO: O S. guttatum possui efeito vasodilatador através da preservação da função endotelial, liberação de NO mediada pelo receptor muscarínico e inibição do movimento de Ca2+, enquanto o efeito depressor do miocárdio atrial pode estar ligado ao receptor muscarínico. Esses achados fornecem a base farmacológica para o uso do extrato de S. guttatum como um medicamento anti-hipertensivo.