Pseudopterosin A Research Articles

Pseudopterosin Aameliorates ischaemia-induced brain injury by acting on Akt signalling pathway.

Brain injury caused by ischaemic stroke is amajor cause of disability and death throughout the world. The present study evaluates the neuroprotective effect of pseudopterosin A(PtA) against ischaemia-induced brain injury. Ischaemia was induced by pMCAO model, and rats were separated in to three groups. Acontrol group; an ischemic group receiving saline solution; and aPtA group receiving PtA (5 mg/kg, i.p.) for the period of three days, i.e. two days before surgery and after the surgery. Effect of PtA was assessed by estimating the infract volume and neurological deficits. Level of oxidative stress, inflammatory mediators, and markers of apoptosis were estimated in the brain tissues. Western blot assay and immunohistochemistry was done for the assessment of expressions of protein. Data from the study suggest that treatment with PtA significantly decreases the infracted volume and neurological deficit score compared to the ischaemic group. Treatments with PtA attenuate the activity of antioxidant enzyme, and the level of inflammatory mediators and markers of apoptosis in the brain tissues of ischaemia-induced brain injury. Phosphorylation of FKHR, Bad, and Akt were significantly reduced in the PtA-treated group compared to the ischaemic group. The present study shows that pseudopterosin Aattenuates neuronal injury in the pMCAO model by acting on the Akt signalling pathway.

Cyclodextrin Formulation of the Marine Natural Product Pseudopterosin A Uncovers Optimal Pharmacodynamics in Proliferation Studies of Human Umbilical Vein Endothelial Cells

Pseudopterosin A (PsA) treatment of growth factor depleted human umbilical vein endothelial cell (HUVEC) cultures formulated in hydroxypropyl-β-cyclodextrin (HPβCD) for 42 h unexpectedly produced a 25% increase in cell proliferation (EC50 = 1.34 × 10−8 M). Analysis of dose response curves revealed pseudo-first order saturation kinetics, and the uncoupling of cytotoxicity from cell proliferation, thereby resulting in a widening of the therapeutic index. The formulation of PsA into HPβCD produced a 200-fold increase in potency over a DMSO formulation; we propose this could result from a constrained presentation of PsA to the receptor, which would limit non-specific binding. These results support the hypothesis that the non-specific receptor binding of PsA when formulated in DMSO has ostensibly masked prior estimates of specific activity, potency, and mechanism. Collectively, these results suggest that the formulation of PsA and compounds of similar chemical properties in HPβCD could result in significant pharmacological findings that may otherwise be obscured when using solvents such as DMSO.

Pseudopterosin A ‐ an Atypical Antagonist of Adenosine A2B Receptors that Accelerates Angiogenesis

SummaryPseudopterosins are known anti‐inflammatory and anti‐microbial agents, isolated from the soft coral, Pseudopterogorgia elisabethae. We report pseudopterosins as activators of cell proliferation in human umbilical vein endothelial cells (HUVEC), a cellular model of angiogenesis. A hydroxypropyl‐β‐cyclodextrin (HPβCD) formulation of pseudopterosin A (PsA) elicited a 25% increase in cell proliferation (EC50 = 1.34 ×10−8 M) in growth factor depleted HUVEC lines. This constitutes a >200 fold increase in potency over DMSO formulations. We demonstrate that the effect of PsA is mediated through inhibition of adenosine A2B receptors which leads to decreased synthesis of cAMP and that this effect can be reversed with a selective A2 agonist, CV‐1808. In addition we show that PsA can induce protein kinase B (AKT) phosphorylation which has been shown to activate proliferation via the phosphatidylinositol 3‐kinase (PI3K) pathway. Collectively, this indicates that pseudopterosins are promising compounds for adenosine receptor mediated pathologies.

Pharmacological characterization of the pseudopterosins: Novel anti-inflammatory natural products isolated from the Caribbean soft coral, Pseudopterogorgia elisabethae

Pseudopterosin E (PSE), a C-10 linked fucose glycoside and pseudopterosin A (PSA), a C-9 xylose glycoside isolated from the marine gorgonian Pseudopterogorgia elisabethae were both effective in reducing PMA-induced mouse ear edema when administered topically (ED 50, (μg/ear) PSE(38), PSA(8)) or systemically (ED 50 (mg/kg, i.p.) PSE (14), PSA (32)). Both compounds exhibited in vivo analgesic activity in phenyl-p-benzoquinone-induced writhing (ED 50 (mg/kg, i.p.) PSE(14), PSA(4). PSE inhibited zymosan-induced writhing (ED 50 = 6 mg/kg, i.p.), with a concomitant dose-dependent inhibition of peritoneal exudate 6-keto-prostaglandin F 1α (ED 50 = 24 mg/kg) and leukotriene C 4 (ED 50 = 24 mg/kg). In vitro, the pseudopterosins were inactive as inhibitors of phospholipase A 2, cyclooxygenase, cytokine release, or as regulators of adhesion molecule expression. PSA inhibited prostaglandin E 2 and leukotriene C 4 production in zymosanstimulated murine peritoneal macrophages (IC 50 = 4 μM and 1 μM, respectively); however, PSE was much less effective. These data suggest that the pseudopterosins may mediate their antiinflammatory effects by inhibiting eicosanoid release from inflammatory cells in a concentration and dose-dependent manner.