Phaleria macrocarpa, commonly known as Mahkota dewa is a medicinal plant that is indigenous to Indonesia and Malaysia. Extracts of P. macrocarpa have been used since years in traditional medicine that are evaluated scientifically as well. The extracts are reported for a number of valuable medicinal properties such as anti-cancer, anti-diabetic, anti-hyperlipidemic, anti-inflammatory, anti-bacterial, anti-fungal, anti-oxidant and vasorelaxant effect. The constituents isolated from different parts of P. macrocarpa include Phalerin, gallic acid, Icaricide C, magniferin, mahkoside A, dodecanoic acid, palmitic acid, des-acetylflavicordin-A, flavicordin-A, flavicordin-D, flavicordin-A glucoside, ethyl stearate, lignans, alkaloids andsaponins. The present review is an up-to-date summary of occurrence, botanical description, ethnopharmacology, bioactivity and toxicological studies related to P. macrocarpa.

D-serine has been implicated as a brain messenger, promoting not only neuronal signalling but also synaptic plasticity. Thus, a sensitive tool for D-serine monitoring in brain is required to understand the mechanisms of D-serine release from glia cells. A biosensor for direct fixed potential amperometric monitoring of D-serine incorporating mammalian D-amino acid oxidase (DAAO) immobilized on a Nafion coated poly-ortho-phenylenediamine (PPD) modified Pt-Ir disk electrode was therefore developed. The combined layers of PPD and Nafion enhanced the enzyme activity and biosensor efficiency by approximately 2-fold compared with each individual layer. A steady state response time (t(90%)) of 0.7+/-0.1s (n=8) and limit of detection 20+/-1 nM (n=8) were obtained. Cylindrical geometry showed lower sensitivity compared to disk geometry (61+/-7 microA cm(-2) mM(-1), (n=4), R(2)=0.999). Interference by ascorbic acid (AA), the main interference species in the central nervous system and other neurochemical electroactive molecules was negligible. Implantation of the electrode and microinjection of D-serine into rat brain striatal extracellular fluid demonstrated that the electrode was capable of detecting D-serine in brain tissue in vivo.

Aim: This study investigated the impact of hypertension combined with diabetic nephropathy on rat renal α₁-adrenoceptor subtype composition. Methods: In streptozotocin-induced diabetic spontaneously hypertensive rats (SHR), diabetic nephropathy developed as reflected by increased kidney index, plasma creatinine, albumin excretion, creatinine clearance and fractional excretion of Na⁺ (all p < 0.05). Renal vasoconstrictions caused by electrical stimulation of renal nerves and intrarenally administered noradrenaline (α-adrenoceptor agonist), phenylephrine (α₁-adrenoceptor agonist) and methoxamine (α_1A-adrenoceptor agonist) were determined in the presence and absence of intrarenally administered amlodipine (Ca²⁺ channel blocker), 5-methylurapidil (α_1A-adrenoceptor antagonist), chloroethylclonidine (α_1B-adrenoceptor antagonist) and BMY 7378 (α_1D-adrenoceptor antagonist). Results: In diabetic nephropathy SHR, there was a significant (all p < 0.05) attenuation of all adrenergically induced vasoconstrictor responses in the antagonists, except chloroethylclonidine, which caused a significant (all p < 0.05) enhancement of the responses. Conclusion: The data demonstrated that there was a functional coexistence of α_1A- and α_1D-adrenoceptors in the renal vasculature of SHR irrespective of the presence of diabetic nephropathy. However, there was a minor contribution of pre-synaptic α-adrenoceptors to the adrenergically mediated vasoconstrictor responses in the diabetic nephropathy SHR.

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Objective: Impairment of vascular reactivity in diabetes may be due to endothelium and/or vascular smooth muscle dysfunction. This study aimed to verify the role of endothelium and vascular smooth muscle in diabetes at different time-course after streptozotocin (STZ) administration.Method: Endothelium-intact and denuded aortic rings obtained from non-diabetic and diabetic rats at different time-course (1-4 weeks) were subjected to graded concentrations of potassium chloride (KCl) and phenylephrine (PE), L-NAME and indomethacin, respectively.Results: Vasoconstrictor responses (maximum contractility, Emax) to KCl in endothelium-intact and denuded aortic rings were significantly influenced at week 4 (P<0.05). In response to PE, Emax values of endothelium-intact and denuded rings significantly decrease as diabetes progresses (P<0.05). The pD2 values were significantly greater in endothelium-denuded than endothelium-intact diabetic aortic rings starting from 2 weeks onwards (P<0.05). In the endothelium intact, PE-induced contractile responses (Emax and pD2) in the presence of L-NAME and indomethacin were significantly greater than PE alone (P<0.05). It was found that the percentage of calcium released from intracellular stores sensitive to PE decreased, due to diabetes.Conclusion: This study clearly demonstrated that the alterations in vascular reactivity to vasoconstrictor phenylephrine were significantly influenced by the duration of diabetes.

Background Vitex pubescens has been used traditionally in hypertension treatment but not yet scientifically assessed. The objective of the study is to investigate the antihypertensive and vasorelaxant activities of V. pubescens , study its underlying pharmacological mechanisms, and identify the relevant vasoactive compounds. Methods Successive extractions of V. pubescens leaf were carried out to produce petroleum ether (VPPE), chloroform (VPCE), methanol (VPME), and water (VPWE) extracts. Spontaneously hypertensive rats (SHRs) received a daily oral administration of the extracts (500 mg/kg/day; n = 6) or verapamil (15 mg/kg/day; n = 6) for 2 weeks, while the systolic and diastolic blood pressures were measured using non-invasive tail-cuff method. Vasorelaxation assays of the extracts were later conducted using phenylephrine (PE, 1 μM) pre-contracted aortic ring preparation. Mechanisms of vasorelaxation by the most potent fraction were studied using vasorelaxation assays with selected blockers/inhibitors. GC-MS was conducted to determine the active compounds. Results VPPE elicited the most significant diminution in systolic and diastolic blood pressure of treated SHRs and produced the most significant vasorelaxation in the aortic rings. Vasorelaxant effects of F2-VPPE were significantly reduced in endothelium-denuded aortic rings by glibenclamide (1 μM), whereas calcium chloride and PE-induced contractions were significantly suppressed. Endothelium removal of the aortic rings or incubation with indomethacin (10 μM), atropine (1 μM), methylene blue (10 μM), propranolol (1μM) and L-NAME (10 μM) did not significantly alter F2-VPPE-induced vasorelaxation. Seven compounds were identified using GC-MS, including spathulenol. Conclusion F2-VPPE exerted its endothelium-independent vasorelaxation by inhibition of vascular smooth muscle contraction induced by extracellular Ca +2 influx through trans-membrane Ca +2 channels and/or Ca +2 release from intracellular stores, and by activation of K ATP channels. The vasorelaxation effects of V. pubescens could be mediated by the compound, spathulenol.