Pharmacological Justification for the Medicinal Use of Plumeria rubra Linn. in Cardiovascular Disorders

Plumeria rubra (L.) is a traditional folkloric medicinal herb used to treat cardiovascular disorders. The present investigation was methodically planned to investigate the pharmacological foundations for the therapeutic effectiveness of P. rubra in cardiovascular illnesses and its underlying mechanisms. Ex vivo vaso-relaxant effects of crude leaf extract of P. rubra were observed in rabbit aorta ring preparations. Hypotensive effects were measured using pressure and force transducers connected to the Power Lab data acquisition system. Furthermore, P. rubra displayed cardioprotective properties in rabbits when they were exposed to adrenaline-induced myocardial infarction. In comparison to the intoxicated group, the myocardial infarction model showed decreased troponin levels, CK-MB, LDH, ALT, ALP, AST, and CRP, as well as necrosis, apoptosis, oedema, and inflammatory cell enrollment. P. rubra has revealed good antioxidant properties and prolonged the noradrenaline intoxicated platelet adhesion. Its anticoagulant, vasorelaxant, and cardioprotective effects in both in vivo and ex vivo investigations are enabled by blocking L-type calcium channels, lowering adrenaline, induced oxidative stress, and tissue tear, justifying its therapeutic utility in cardiovascular disorders.

Antiangiogenic Activity and in Silico Cereblon Binding Analysis of Novel Thalidomide Analogs

Due to its antiangiogenic and anti-immunomodulatory activity, thalidomide continues to be of clinical interest despite its teratogenic actions, and efforts to synthesize safer, clinically active thalidomide analogs are continually underway. In this study, a cohort of 27 chemically diverse thalidomide analogs was evaluated for antiangiogenic activity in an ex vivo rat aorta ring assay. The protein cereblon has been identified as the target for thalidomide, and in silico pharmacophore analysis and molecular docking with a crystal structure of human cereblon were used to investigate the cereblon binding abilities of the thalidomide analogs. The results suggest that not all antiangiogenic thalidomide analogs can bind cereblon, and multiple targets and mechanisms of action may be involved.

Antimicrobial, Antioxidant and Antihypertensive Activities of Major Bioactive Compounds from The Stems of Crossostephium chinense L.

Crossostephium chinense L. or Hai-Fu-Rung as a new source of herbal medicine was naturally grows near coastal areas on limestone and coral formations in Taiwan and South east of Asia’s region. This plant is one of the famous TCM (Traditional China Medicine) that traditionally used for treating colds, measles, rheumatic, and bronchitis. Extract of whole plant of C. chinense have been reported to exhibit diverse biological activities such as anti-proliferative, hepatoprotective, and anti-inflammation with ameliorative effect, but only a few of these studies involved as antimicrobial, antioxidant, and antihypertensive agent especially from stem part. Interestingly, even C. chinense is a famous herbal medicine, but it still rare, threatened in the wild, and need further investigation especially for its stem part. Hence, this study was conducted to investigate the major of this plant. First result of this study was obtained nine major compounds from crude methanol extract of this plant and identified as: lupeol, b-sitostenone, octadecyl (E)-p-coumarate, cycloeucalenol, oleanolic acid, ursolic acid, stigmastan-3-one, betulin, and ergone. Furthermore, some biological assays such as antimicrobial, antioxidant and antihypertensive activities were evaluated by inhibitory assay; DPPH, FTC, and TBA assays; and ACE inhibitory assay, respectively. Rat aorta ring assay also could be used for completely understanding of antihypertensive effect from air dried stems of C. chinense.

The integrin-binding defective FGF2 mutants potently suppress FGF2 signalling and angiogenesis

We recently found that integrin αvβ3 binds to fibroblast growth factor (FGF)-αvβ31 (FGF1), and that the integrin-binding defective FGF1 mutant (Arg-50 to glutamic acid, R50E) is defective in signalling and antagonistic to FGF1 signalling. R50E suppressed angiogenesis and tumour growth, suggesting that R50E has potential as a therapeutic. However, FGF1 is unstable, and we had to express R50E in cancer cells for xenograft study, since injected R50E may rapidly disappear from circulation. We studied if we can develop antagonist of more stable FGF2. FGF2 is widely involved in important biological processes such as stem cell proliferation and angiogenesis. Previous studies found that FGF2 bound to αvβ3 and antagonists to αvβ3 suppressed FGF2-induced angiogenesis. However, it is unclear how FGF2 interacts with integrins. Here, we describe that substituting Lys-119/Arg-120 and Lys-125 residues in the predicted integrin-binding interface of FGF2 to glutamic acid (the K119E/R120E and K125E mutations) effectively reduced integrin binding to FGF2. These FGF2 mutants were defective in signalling functions (ERK1/2 activation and DNA synthesis) in NIH3T3 cells. Notably they suppressed, FGF2 signalling induced by WT FGF2 in endothelial cells, suggesting that the FGF2 mutants are antagonists. The FGF2 mutants effectively suppressed tube formation in vitro, sprouting in aorta ring assays ex vivo and angiogenesis in vivo. The positions of amino acids critical for integrin binding are different between FGF1 and FGF2, suggesting that they do not interact with integrins in the same manner. The newly developed FGF2 mutants have potential as anti-angiogenic agents and useful tools for studying the role of integrins in FGF2 signalling.

Cardioprotective Effects of Voluntary Exercise in a Rat Model: Role of Matrix Metalloproteinase-2

Background. Regular exercise at moderate intensity reduces cardiovascular risks. Matrix metalloproteinases (MMPs) play a major role in cardiac remodeling, facilitating physiological adaptation to exercise. The aim of this study was to examine the influence of voluntary physical exercise on the MMP-2 enzyme activity and to investigate the cardiac performance by measurement of angina susceptibility of the heart, the basal blood pressure, the surviving aorta ring contraction, and the cardiac infarct size after I/R-induced injury.Methods. Male Wistar rats were divided into control and exercising groups. After a 6-week period, the serum level of MMP-2, basal blood pressure, cardiac angina susceptibility (the ST segment depression provoked by epinephrine and 30 s later phentolamine), AVP-induced heart perfusion and aorta ring contraction, infarct size following 30 min ischemia and 120 min reperfusion, and coronary effluent MMP-2 activity were measured.Results. Voluntary wheel-running exercise decreased both the sera (64 kDa and 72 kDa) and the coronary effluent (64 kDa) MMP-2 level, reduced the development of ST depression, improved the isolated heart perfusion, and decreased the ratio of infarct size.Conclusion. 6 weeks of voluntary exercise training preserved the heart against cardiac injury. This protective mechanism might be associated with the decreased activity of MMP-2.

Evaluation of the Anti-angiogenic Activity of Saponins from Maesa lanceolata by Different Assays

Angiogenesis, in which a vascular network is established from pre-existing vessels, is a complex multistep process. Mechanisms underlying angiogenesis can be investigated using a variety of in vitro, ex vivo and in vivo approaches. Evaluation of several promising plants and plant metabolites, including terpenoids, revealed promising anti-angiogenic activity. Since the maesasaponins displayed anti-angiogenic activity in the chick chorioallantoic membrane (CAM) assay, their activity was further investigated in several test systems. The rat aorta ring assay was compared with the placental vein assay and then selected for the ex vivo investigation of the saponins. Besides their effect on the viability of HUVEC, the anti-angiogenic capacity of the compounds was also investigated in an in vivo zebrafish assay. The activity of the saponins in the viability assay was more pronounced than in the rat aorta ring assay and similar to the effect observed in the CAM assay. The use of different test systems, however, implies different results in the case of saponins.

Evaluation of the Possible Mechanisms of Antihypertensive Activity ofLoranthus micranthus: An African Mistletoe

Loranthus micranthus (LM), also called African mistletoe is a major NigerianLoranthaceaeplant used traditionally to treat hypertension. The methanolic leaf extract of the plant (LMME) has been shown to elicit anti-hypertensive activity in rats but mechanism remains unclear. This study was undertaken to study the effect of LM on pressor-induced contraction of rat aorta smooth muscles and serum lipid profiles in mice. The LMME was partitioned to produce n-butanol (NBF-LMME), chloroform (CF-LMME), ethyl acetate (EAF-LMME) and water (WF-LMME) fractions. The median effective concentrations and maximum relaxation of the fractions were determined against epinephrine and KCl pre-contracted rat aorta ring model. Serum lipid profiles and nitric oxide (NO) were determined spectrophotometrically in mice administered per orally 250 mg/kg b.w. of each fraction for 21 days. Data were analyzed statistically. NBF-LMME elicited the highest dose-dependent inhibitory effect on rat aorta pre-contracted with norepinephrine and KCl, followed in decreasing order by WF-LMME > CF-LMME > EAF-LMME. Similar order of activity was observed in the ability of these fractions to inhibit elevation in artherogenic lipids, raise serum nitric oxide and reduce cardiac arginase in mice. We conclude the anti-hypertensive activity ofL. micranthusinvolve anti-artherogenic events, vasorelaxation, cardiac arginase reduction and NO elevation.